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Broadly targeted human cytomegalovirus-specific CD4 + and CD8 + T cells dominate the memory compartments of exposed subjects
Open accessAbstract
Human cytomegalovirus (HCMV) infections of immunocompetent hosts are characterized by a dynamic, life-long interaction in which host immune responses, particularly of T cells, restrain viral replication and prevent disease but do not eliminate the virus or preclude transmission. Because HCMV is among the largest and most complex of known viruses, the T cell resources committed to maintaining this balance have never been characterized completely. Here, using cytokine flow cytometry and 13,687 overlapping 15mer peptides comprising 213 HCMV open reading frames (ORFs), we found that 151 HCMV ORFs were immunogenic for CD4+ and/or CD8+ T cells, and that ORF immunogenicity was influenced only modestly by ORF expression kinetics and function. We further documented that total HCMV-specific T cell responses in seropositive subjects were enormous, comprising on average ∼10% of both the CD4+ and CD8+ memory compartments in blood, whereas cross-reactive recognition of HCMV proteins in seronegative individuals was limited to CD8+ T cells and was rare. These data provide the first glimpse of the total human T cell response to a complex infectious agent and will provide insight into the rules governing immunodominance and cross-reactivity in complex viral infections of humans.
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“Infection with CMV causes a large accumulation of virus-specific memory T cells, so that approximately 10 % of the CD4+ and CD8+ T cell pool becomes specific for this virus (Sylwester et al. 2005).”
From Is immunosenescence influenced by our lifetime “dose” of exercise? (2016) · cites this paper as Sylwester et al. 2005
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“It is therefore currently unknown whether values such as 10 % of the CD4+ and CD8+ T cell pool being specific for CMV is above, or below, the ideal threshold (Sylwester et al. 2005).”
From Is immunosenescence influenced by our lifetime “dose” of exercise? (2016) · cites this paper as Sylwester et al. 2005
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BackgroundImpact of Aging and Cytomegalovirus on Immunological Response to Influenza Vaccination and Infection
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“In healthy human adults, an average of 5% of all CD8+ T cells are specific for CMV [14], and the frequencies can”
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“portant to realize that the current study, while having avoided the limitations of the small array of currently available class I HLA multimers, is still very restricted in the sense that it has addressed only two, albeit immunodominant, of the >200 open reading frames of CMV (45).”
BackgroundDirect and Indirect Effects of Cytomegalovirus-Induced γδ T Cells after Kidney Transplantation
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“The general absence of HCMV disease imposes an extraordinarily large immunological burden on its infected hosts because almost 10% of memory CD4 and CD8 T cells are specific to HCMV antigens (1).”
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BackgroundEpidemiologic Analysis of Reactivated Cytomegalovirus Antigenemia in Patients with Cancer
Han, X. Y. (2007) · Journal of Clinical Microbiology · doi:10.1128/jcm.01670-06 · Cited by 79
“A recent study with peptides spanning the entire CMV proteome and cytokine flow cytometry found that the human immune system dedicates 10% of the memory repertoire of CD4 and CD8 T cells to keep the virus in check ( 21 ).”
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Mana, H. A., Yassine, H. M., Younes, N., Al-Mohannadi, A., Al‐Sadeq, D. W., Alhababi, D., Nasser, E. A. A., & Nasrallah, G. K. (2019) · Pathogens · doi:10.3390/pathogens8040213 · Cited by 78
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“There have been a number of approaches taken to design virus vectors from the virus family Herpesviridae, which consists of large DNA viruses that can establish long, latent, and often asymptomatic infections [110].”
BackgroundThe two faces of heterologous immunity: protection or immunopathology
Sharma, S., & Thomas, P. G. (2013) · Journal of Leukocyte Biology · doi:10.1189/jlb.0713386 · Cited by 77
Controlling Cytomegalovirus: Helping the Immune System Take the Lead
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“Antigen recognition by CD4+ T cells is similar to CD8+ T cells in that T cells recognizing pp65 are some of the most abundant but T cells recognizing other antigens such as gB, UL86, pp28, IE-2, UL36, UL48, pp10, UL113, and IRS-1 are also highly abundant [56].”
Immunotherapy for transplantation-associated viral infections
Roddie, C., & Peggs, K. S. (2017) · Journal of Clinical Investigation · doi:10.1172/jci90599 · Cited by 75
“CMV-seropositive subjects recognize a median of 12 (CD4) and 8 (CD8) CMV ORFs, which amounts to a circulating CMV memory repertoire of greater than 20% in at least one-third of older subjects (26).”
BackgroundMechanisms of immunosenescence: lessons from models of accelerated immune aging
Saux, S. L., Weyand, C. M., & Goronzy, J. J. (2012) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2011.06297.x · Cited by 76
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“The potential for CD8 T cells to simultaneously produce TNF- and IFN- has been observed in acute MCMVinfected adult mice and in healthy HCMV-infected individuals (50, 53, 54).”
BackgroundBrenchley, J. M., Ruff, L. E., Casazza, J. P., Koup, R. A., Price, D. A., & Douek, D. C. (2006) · Journal of Virology · doi:10.1128/jvi.00070-06 · Cited by 75
“While these proteins are immunostimulatory in many individuals, this stimulation protocol invariably results in an underrepresentation of the total CMV-specific CD4 T-cell population ( 40 ).”
BackgroundViral inoculum dose impacts memory T ‐cell inflation
Redeker, A., Welten, S. P. M., & Arens, R. (2013) · European Journal of Immunology · doi:10.1002/eji.201343946 · Cited by 74
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“For example, CMV-specific T-cell responses are 3–5 fold higher in HIV-positive individuals and it is estimated that 20–25% of residual immune activation in HIV is due to CMV-specific T-cell responses [32,33].”
BackgroundWalton, S. M., Wyrsch, P., Munks, M. W., Zimmermann, A., Hengel, H., Hill, A. B., & Oxenius, A. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.181.2.1128 · Cited by 73
“Although HCMV-specific CD4 T cell epitopes were described previously (9), longitudinal analysis of CD4 T cell responses in humans is often limited to patients undergoing organ transplantation (5, 10), due to the fact that primary infection is clinically silent in healthy individuals and hence usually undiagnosed.”
BackgroundImpact of CMV upon immune aging: facts and fiction
Jergović, M., Contreras, N. A., & Nikolich-Žugich, J. (2019) · Medical Microbiology and Immunology · doi:10.1007/s00430-019-00605-w · Cited by 73
Cytomegalovirus in the Neonate: Immune Correlates of Infection and Protection
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Diverse Specificities, Phenotypes, and Antiviral Activities of Cytomegalovirus-Specific CD8+T Cells
Jackson, S. E., Mason, G. M., Okecha, G., Sissons, J. G. P., & Wills, M. R. (2014) · Journal of Virology · doi:10.1128/jvi.01477-14 · Cited by 74
“in 2005 (16) examined the CD8 and CD4 T cell responses in a cohort of 33 individuals chosen to represent a wide variety of ethnic and HLA backgrounds.”
BackgroundThe Context of Gene Expression Defines the Immunodominance Hierarchy of Cytomegalovirus Antigens
Dekhtiarenko, I., Jarvis, M. A., Ruzsics, Z., & Čičin‐Šain, L. (2013) · The Journal of Immunology · doi:10.4049/jimmunol.1203173 · Cited by 73
“Human CMV (HCMV) induces a potent cellular immune response, which can dominate the memory compartment of the infected patients (2).”
BackgroundNakamura, R., Rosa, C. L., Longmate, J., Drake, J., Slape, C., Zhou, Q., Lampa, M. G., O'Donnell, M. R., Cai, J., Farol, L., et al. (2015) · The Lancet Haematology · doi:10.1016/s2352-3026(15)00246-x · Cited by 73
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“Primary diagnosis Acute myelogenous leukemia 19 (37) 14 (27) Acute lymphoblastic leukemia 11 (22) 6 (12) Myelodysplastic syndrome 8 (16) 11 (22) Non-Hodgkin lymphoma 6 (12) 10 (20) Myeloproliferative disease 5 (10) 5 (10) Acute leukemia NOS 1 (2) 3 (6) Hodgkin lymphoma 1 (2) 2 (4)”
Gianella, S., Massanella, M., Richman, D. D., Little, S. J., Spina, C. A., Vargas, M. V., Lada, S. M., Daar, E. S., Dubé, M. P., Haubrich, R., et al. (2014) · Journal of Virology · doi:10.1128/jvi.00831-14 · Cited by 72
“Along with HIV itself, CMV could be an important mediator of immune activation, especially because a large fraction of an infected person’s immune repertoire is targeted toward CMV (40, 41), and CMV reactivation in the genital tract is common, even in subjects with high CD4 T cell counts during ART (42).”
BackgroundAdoptive T‐cell immunotherapy for ganciclovir‐resistant CMV disease after lung transplantation
Holmes‐Liew, C., Holmes, M., Beagley, L., Hopkins, P. M.-A., Chambers, D. C., Smith, C., & Khanna, R. (2015) · Clinical & Translational Immunology · doi:10.1038/cti.2015.5 · Cited by 72
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“…dynamics of most chronic viral infections such as HIV, hepatitis B and C, and cytomegalovirus are assessed by serially sampling blood using polymerase chain reaction (Perelson et al., 1996), and by ex vivo quantitation of circulating lymphocytes to estimate immune response (Sylwester et al., 2005).”
MethodCMV pp65 and IE-1 T cell epitopes recognized by healthy subjects
Slezak, S. L., Bettinotti, M. P., Selleri, S., Adams, S. D., Marincola, F. M., & Stroncek, D. F. (2007) · Journal of Translational Medicine · doi:10.1186/1479-5876-5-17 · Cited by 72
“In addition, they found that CD8+ T cell responses to both pp65 and IE-1 were strong and the CD4+ T cell responses were strong to pp65 but weak to IE1 which supports the results of our study [25].”
BackgroundResultCytomegalovirus Infection and Memory T Cell Inflation
Kim, J., Kim, A.-R., & Shin, E. (2015) · Immune Network · doi:10.4110/in.2015.15.4.186 · Cited by 72
“However, robust CD8 T cell responses are observed in CMV-infected hosts (21-23).”
BackgroundDifferential Impact of Age and Cytomegalovirus Infection on the γδ T Cell Compartment
Roux, A., Mourin, G., Larsen, M., Fastenackels, S., Urrutia, A., Gorochov, G., Autran, B., Donner, C., Sidi, D., Sibony-Prat, J., et al. (2013) · The Journal of Immunology · doi:10.4049/jimmunol.1202940 · Cited by 68
“These cells can occupy up to 40% of the entire T cell memory pool (5), thus altering significantly the balance between the naive and memory T cell”
BackgroundBiology and pathogenesis of cytomegalovirus in periodontal disease
Contreras, A., Botero, J. E., & Slots, J. (2013) · Periodontology 2000 · doi:10.1111/j.1600-0757.2012.00448.x · Cited by 71
“specific responses are prominent in a small number (<5%) of individuals (156).”
BackgroundHoltappels, R., Böhm, V., Podlech, J., & Reddehase, M. J. (2008) · Medical Microbiology and Immunology · doi:10.1007/s00430-008-0093-2 · Cited by 71
The aging bone marrow and its impact on immune responses in old age
Pritz, T., Weinberger, B., & Grubeck‐Loebenstein, B. (2014) · Immunology Letters · doi:10.1016/j.imlet.2014.06.016 · Cited by 71
Lymph Node Macrophages Restrict Murine Cytomegalovirus Dissemination
Farrell, H. E., Davis-Poynter, N. J., Bruce, K. L., Lawler, C., Dölken, L., Mach, M., & Stevenson, P. G. (2015) · Journal of Virology · doi:10.1128/jvi.00480-15 · Cited by 72
Human cytomegalovirus vaccine: time to look for alternative options
Khanna, R., & Diamond, D. J. (2005) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2005.11.006 · Cited by 70
Cook, C. H., & Trgovcich, J. (2011) · Antiviral Research · doi:10.1016/j.antiviral.2011.03.179 · Cited by 70
“For CD8 T-cells, some hosts develop “inflationary” CMV-specific memory responses that grow to occupy very large percentages of the T-memory compartment (Gillespie et al., 2000; Holtappels et al., 2002; Karrer et al., 2003; Karrer et al., 2004; Olsson et al., 2001; Ouyang et al., 2003; Reddehase et al., 1985; Sierro et…”
BackgroundTuuminen, T., Kekäläinen, E., Mäkelä, S., Ala-Houhala, I. O., Ennis, F. A., Hedman, K., Mustonen, J. T., Vaheri, A. I., & Arstila, T. P. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.179.3.1988 · Cited by 70
“For example, a global analysis of CMV-specific memory T cells in humans has shown that on the average they account for 10% of the total memory population, but in some individuals this fraction may be up to 40% (46).”
BackgroundSchleiss, M. R., Lacayo, J. C., Belkaid, Y., McGregor, A., Stroup, G., Rayner, J., Alterson, K. D., Chulay, J. D., & Smith, J. (2007) · The Journal of Infectious Diseases · doi:10.1086/511982 · Cited by 70
Adler, S. P., Lewis, N. M., Conlon, A., Christiansen, M. P., Al-Ibrahim, M. S., Rupp, R. E., Fu, T., Bautista, O. M., Tang, H., Wang, D., et al. (2019) · The Journal of Infectious Diseases · doi:10.1093/infdis/jiz141 · Cited by 70
Munks, M. W., Pinto, A. K., Doom, C. M., & Hill, A. B. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.178.11.7235 · Cited by 70
Dekhtiarenko, I., Ratts, R. B., Blatnik, R., Lee, L. N., Fischer, S., Borkner, L., Oduro, J. D., Marandu, T. F., Hoppe, S., Ruzsics, Z., et al. (2016) · PLoS Pathogens · doi:10.1371/journal.ppat.1006072 · Cited by 68
The T cell response to persistent herpes virus infections in common variable immunodeficiency
Raeiszadeh, M., Kopycinski, J., Paston, S. J., Diss, T. C., Lowdell, M. W., Hardy, G. A. D., Hislop, A. D., Workman, S., Dodi, A. I., Emery, V. C., et al. (2006) · Clinical & Experimental Immunology · doi:10.1111/j.1365-2249.2006.03209.x · Cited by 69
Enhanced antiglioma activity of chimeric HCMV/HSV-1 oncolytic viruses
Shah, A. C., Parker, J. N., Gillespie, G. Y., Lakeman, F. D., Meleth, S., Markert, J. M., & Cassady, K. A. (2007) · Gene Therapy · doi:10.1038/sj.gt.3302942 · Cited by 68
High Throughput T Epitope Mapping and Vaccine Development
Pira, G. L., Ivaldi, F., Moretti, P., & Manca, F. (2010) · BioMed Research International · doi:10.1155/2010/325720 · Cited by 68
Associations between Virologic and Immunologic Dynamics in Blood and in the Male Genital Tract
Gianella, S., Strain, M. C., Rought, S. E., Vargas, M. V., Little, S. J., Richman, D. D., Spina, C. A., & Smith, D. M. (2011) · Journal of Virology · doi:10.1128/jvi.06077-11 · Cited by 68
“Moreover, asymptomatic CMV coinfection is associated with higher T-cell immune activation (32, 36, 48, 71), which is linked to blunted CD4 cell recovery during antiretroviral therapy and to premature mortality (29, 35, 36).”
BackgroundResultTormo, N., Solano, C., Benet, I., Nieto, J. B., de la Cámara, R., López, J., Noblejas, A. G., Muñoz‐Cobo, B., Costa, E., Clari, M. Á., et al. (2011) · Bone Marrow Transplantation · doi:10.1038/bmt.2010.330 · Cited by 68
Costa-García, M., Ataya, M., Moraru, M., Vilches, C., López‐Botet, M., & Muntasell, A. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.00687 · Cited by 64
“, HLA-DR7) (Supplementary Table I) (45).”
BackgroundRossini, G., Cerboni, C., Santoni, A., Landini, M. P., Landolfo, S., Gatti, D., Gribaudo, G., & Varani, S. (2012) · Mediators of Inflammation · doi:10.1155/2012/607276 · Cited by 74
“and memory T cells develop during acute HCMV infection [94, 95] and robust adaptive immune responses develop to many HCMV antigens, of which IE1 is a significant target of CD4+ and CD8+ T-cell responses [94].”
BackgroundBarabas, S., Spindler, T., Kiener, R., Tonar, C., Lugner, T., Batzilla, J., Bendfeldt, H., Rascle, A., Asbach, B., Wagner, R., et al. (2017) · BMC Immunology · doi:10.1186/s12865-017-0195-y · Cited by 67
Jackson, S. E., Sedikides, G. X., Okecha, G., Poole, E. L., Sinclair, J. H., & Wills, M. R. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.00733 · Cited by 66
Lakshmikanth, T., Olin, A., Chen, Y., Mikeš, J., Fredlund, E., Remberger, M., Omazic, B., & Brodin, P. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.08.021 · Cited by 64
A Perspective on the Role of Computational Models in Immunology
Chakraborty, A. K. (2017) · Annual Review of Immunology · doi:10.1146/annurev-immunol-041015-055325 · Cited by 66
Siedner, M. J. (2017) · Journal of Aging and Health · doi:10.1177/0898264317724549 · Cited by 68
“…immune activation caused by direct HIV infection of end-organ tissues (Dube et al., 2008; Eugenin et al., 2008) and coinfections (Hunt et al., 2008; Sylwester et al., 2005; Wilson et al., 2014) is thought to precipitate chronic activation of both innate and adaptive immunologic pathways (Boasso &…”
BackgroundSottile, R., Panjwani, M. K., Lau, C. M., Daniyan, A. F., Tanaka, K., Barker, J. N., Brentjens, R. J., Sun, J. C.-Y., Luduec, J.-B. L., & Hsu, K. C. (2021) · Science Immunology · doi:10.1126/sciimmunol.abe6968 · Cited by 67
Cytomegalovirus-Specific T Cell Immunity Is Maintained in Immunosenescent Rhesus Macaques
Čičin‐Šain, L., Sylwester, A. W., Hagen, S. I., Siess, D. C., Currier, N., Legasse, A. W., Fischer, M. B., Koudelka, C. W., Axthelm, M. K., Nikolich‐Žugich, J., et al. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1100560 · Cited by 67
“CMV is among the most immunogenic of known viruses, eliciting stable frequencies of specific T cells in CMV adults that average 10% of both the CD4 and CD8 memory compartments in blood (18).”
BackgroundSelf-citationThe Immunology of Posttransplant CMV Infection
Carbone, J. (2016) · Transplantation · doi:10.1097/tp.0000000000001095 · Cited by 66
“At around 4 to 6weeks after the primary infection, a diverse T-cell response develops in which broadly targeted CMV-specific CD4 and CD8 cells dominate the memory cell subset and are adequate to achieve viral control in healthy individuals.(18) In vivo data have shown that CMV-specific CD8 T cells are largely responsi…”
BackgroundTurner, J. E., & Brum, P. C. (2017) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2017/4234765 · Cited by 66
“It is however well established that in CMV-seropositive individuals, approximately 10% of the CD4+ and CD8+ T cell pool becomes speci fi c for this virus [84].”
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The emerging role of ECM crosslinking in T cell mobility as a hallmark of immunosenescence in humans
Moreau, J.-F., Pradeu, T., Grignolio, A., Nardini, C., Castiglione, F., Tieri, P., Capri, M., Salvioli, S., Taupin, J.-L., Garagnani, P., et al. (2017) · Ageing Research Reviews · doi:10.1016/j.arr.2016.11.005 · Cited by 67
Aging, cancer, and antitumor immunity
Ikeda, H., & Togashi, Y. (2021) · International Journal of Clinical Oncology · doi:10.1007/s10147-021-01913-z · Cited by 65
Epigenetic quantification of immunosenescent CD8+ TEMRA cells in human blood
Salumets, A., Tserel, L., Rumm, A. P., Türk, L., Kingo, K., Saks, K., Oras, A., Uibo, R., Tamm, R., Peterson, H., et al. (2022) · Aging Cell · doi:10.1111/acel.13607 · Cited by 70
“Frequent reactivation of latent cytomegalovirus (CMV) repetitively stimulates CD8+ T- cells, increasing their population size (Pawelec, 2014; Sylwester et al., 2005).”
BackgroundMultiple sclerosis – a response-to-damage model
Hart, B. A. ‘., Hintzen, R. Q., & Laman, J. D. (2009) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2009.04.001 · Cited by 66
The role of the thymus in immunosenescence: lessons from the study of thymectomized individuals
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CMV-specific immune reconstitution following allogeneic stem cell transplantation
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Role of T‐Cell Dysfunction, Inflammation, and Coagulation in Microvascular Disease in HIV
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Immunosenescence in atherosclerosis: A role for chronic viral infections
Talepoor, A. G., & Doroudchi, M. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.945016 · Cited by 65
Human CD4+T Cell Response to Human Herpesvirus 6
Nastke, M.-D., Becerra, A., Yin, L., Domínguez-Amorocho, O. A., Gibson, L. L., Stern, L. J., & Calvo‐Calle, J. M. (2012) · Journal of Virology · doi:10.1128/jvi.06573-11 · Cited by 64
Hart, B. A. ‘., & Massacesi, L. (2009) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0b013e31819f1d24 · Cited by 65
“About 25% of the anti-CMV reactivity of CD4 memory T cells is directed against the UL86 open reading frameYencoded major capsid protein (71), which shares a mimicry motif with MOG34Y56 (44).”
BackgroundCellular defense against latent colonization foiled by human cytomegalovirus UL138 protein
Lee, S. H., Albright, E. R., Lee, J.-H., Jacobs, D., & Kalejta, R. F. (2015) · Science Advances · doi:10.1126/sciadv.1501164 · Cited by 65
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Understanding the Failure of CD8+T-Cell Vaccination against Simian/Human Immunodeficiency Virus
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Functional Exhaustion Limits CD4+and CD8+T-Cell Responses to Congenital Cytomegalovirus Infection
Huygens, A., Lecomte, S., Tackoen, M., Olislagers, V., Delmarcelle, Y., Burny, W., Rysselberge, M. V., Liesnard, C., Larsen, M., Appay, V., et al. (2015) · The Journal of Infectious Diseases · doi:10.1093/infdis/jiv071 · Cited by 65
“peptides derived from 10 immunodominant and subdominant CMV proteins [26].”
BackgroundAging, sex, inflammation, frailty, and CMV and HIV infections
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Metadata
- Authors
- Sylwester, A. W., Mitchell, B. L., Edgar, J. B., Taormina, C., Pelte, C., Ruchti, F., Sleath, P. R., Grabstein, K. H., Hosken, N. A., Kern, F., Nelson, J. A., & Picker, L. J.
- Affiliations
- Oregon National Primate Research Center (US)
- Corixa Corporation (US)
- Stiftung Charité (DE)
- Venue
- The Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 2005-09-05
- Volume
- 202
- Issue
- 5
- Pages
- 673-685
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- PMC
- PMC2212883
- OpenAlex
- W2103849595
- Cited by
- 1,339
- References
- 41
- Citations by year
- 2026: 39 · 2025: 53 · 2024: 56 · 2023: 41 · 2022: 56 · 2021: 70 · 2020: 67 · 2019: 81 · 2018: 71 · 2017: 86 · 2016: 74 · 2015: 77 · 2014: 56 · 2013: 83 · 2012: 64
- FWCI
- 38.39
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Experimental Medicine (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (RR 00163, AI21640)
- National Institute of Allergy and Infectious Diseases (R01AI047606, AI 47606, R01AI021640)
- National Center for Research Resources (P51RR000163, M01RR000334)
- Topics
- Health Sciences › Medicine › Epidemiology › Cytomegalovirus and herpesvirus research
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › vaccines and immunoinformatics approaches
- Keywords
- human cytomegalovirus, CD4+ T cells, CD8+ T cells, immunodominance, seropositive individuals, viral persistence
- MeSH terms
- Adult, Cytomegalovirus Infections, Cytomegalovirus, Female, Flow Cytometry, Humans, Immunogenetics, Immunologic Memory, Male, Middle Aged, Peptides, Serologic Tests, CD4-Positive T-Lymphocytes, Open Reading Frames, CD8-Positive T-Lymphocytes
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