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SCIMP, a Transmembrane Adaptor Protein Involved in Major Histocompatibility Complex Class II Signaling
Open accessAbstract
Formation of the immunological synapse between an antigen-presenting cell (APC) and a T cell leads to signal generation in both cells involved. In T cells, the lipid raft-associated transmembrane adaptor protein LAT plays a central role. Its phosphorylation is a crucial step in signal propagation, including the calcium response and mitogen-activated protein kinase activation, and largely depends on its association with the SLP76 adaptor protein. Here we report the discovery of a new palmitoylated transmembrane adaptor protein, termed SCIMP. SCIMP is expressed in B cells and other professional APCs and is localized in the immunological synapse due to its association with tetraspanin-enriched microdomains. In B cells, it is constitutively associated with Lyn kinase and becomes tyrosine phosphorylated after major histocompatibility complex type II (MHC-II) stimulation. When phosphorylated, SCIMP binds to the SLP65 adaptor protein and also to the inhibitory kinase Csk. While the association with SLP65 initiates the downstream signaling cascades, Csk binding functions as a negative regulatory loop. The results suggest that SCIMP is involved in signal transduction after MHC-II stimulation and therefore serves as a regulator of antigen presentation and other APC functions.
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BLNK is a central adaptor downstream of BCR, and PLCG2 is a major BCR proximal signaling node implicated in germinal center and memory B cell formation.
“Two further loci provide more direct mechanistic links to B cell receptor (BCR) signaling: BLNK is a central adaptor downstream of the BCR, and PLCG2 is a major BCR proximal signaling node implicated in germinal center and memory B cell formation.”
From Is there a role for B cells in Alzheimer's disease? (2026) · cites this paper as [26]
The Introduction identifies SLP65 as BLNK and describes its role in BCR signal transduction, including its association with PLC-γ2. The Discussion also reports PLC-γ2 phosphorylation in a SCIMP signaling experiment. Neither passage links PLC-γ2 to germinal center or memory B cell formation. (LLM, conf=0.88)
Experimental — accuracy not yet measuredSeveral AD GWAS loci implicate B cell relevant genes including SCIMP, BLNK, PLCG2, HLA class II region and IGHG1.
“Indeed, several AD GWAS loci implicate B cell relevant genes as well, albeit with varying strength of evidence and confidence in causal gene assignment. These include SCIMP , BLNK , PLCG2 , HLA class II region and IGHG1 [26 -32].”
From Is there a role for B cells in Alzheimer's disease? (2026) · cites this paper as [26]
The Abstract and Results (pages not provided) establish that SCIMP is expressed in B cells and participates in MHC-II signaling, supporting its description as B-cell-relevant. The paper does not report Alzheimer’s disease GWAS loci or establish that any of the listed genes is implicated by such a locus. (LLM, conf=0.87)
Experimental — accuracy not yet measuredSCIMP is expressed across myeloid and B cell lineages and has been identified as an AD-associated locus.
“SCIMP is expressed accross myeloid and B cell lineages and has been identified as an AD-associated locus.”
From Is there a role for B cells in Alzheimer's disease? (2026) · cites this paper as [26]
The Results (page not provided) report SCIMP expression in B cells, monocytes, and monocyte-derived dendritic cells, supporting the expression claim. The passages from our copy do not identify SCIMP as an AD-associated locus; a search for that association found no supporting passage. (LLM, conf=0.87)
Experimental — accuracy not yet measuredHLA class II locus encompassing HLA-DRB1/HLA-DQA1 is a well established AD risk locus, although extensive linkage disequilibrium makes it difficult to pin down the specific causal gene.
“The HLA class II locus encom passing HLA-DRB1/HLA-DQA1 is also a well established AD risk locus, although extensive linkage disequilibrium across this region makes it difficult to pin down the specific causal gene.”
From Is there a role for B cells in Alzheimer's disease? (2026) · cites this paper as [26]
The Introduction and Discussion discuss MHC class II signaling and SCIMP, not Alzheimer’s disease genetics. Searches for HLA-DRB1/HLA-DQA1, an AD risk locus, and linkage disequilibrium found no passage addressing the claimed association or difficulty identifying a causal gene; the retrieved Methods and References passages do not address it either. No page numbers were available in our copy. (LLM, conf=0.76)
Experimental — accuracy not yet measuredIGHG1 is less well established as a causal AD gene and is more accurately described as residing within an AD associated locus rather than as a validated risk gene.
“IGHG1 , in contrast, is less well established as a causal AD gene and is more accurately described as residing within an AD associated locus rather than as a validated risk gene.”
From Is there a role for B cells in Alzheimer's disease? (2026) · cites this paper as [26]
The Introduction, Results, and Discussion passages address SCIMP and MHC-II signaling, not IGHG1 or Alzheimer’s disease. Searches for IGHG1, Alzheimer’s disease, and an AD-associated genetic locus found no passage addressing whether IGHG1 is a causal or validated risk gene. (LLM, conf=0.76)
Experimental — accuracy not yet measured
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Lu, Q., Powles, R. L., Abdallah, S., Ou, D., Wang, Q., Hu, Y., Lu, Y., Liu, W., Li, B., Mukherjee, S., et al. (2017) · PLOS Genetics · doi:10.1371/journal.pgen.1006933 · Cited by 97
Is there a role for B cells in Alzheimer's disease?
Charavner, E.-L., Fillatreau, S., & El Behi, M. (2026) · Cellular Immunology · doi:10.1016/j.cellimm.2026.105154
Metadata
- Authors
- Draber, P., Vonkova, I., Stepanek, O., Hrdinka, M., Kucova, M., Skopcova, T., Otahal, P., Angelisova, P., Horejsi, V., Yeung, M., Weiss, A., & Brdicka, T.
- Affiliations
- Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Prague 14220, Czech Republic
- Czech Academy of Sciences (CZ)
- Howard Hughes Medical Institute (US)
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 2011-11-01
- Volume
- 31
- Issue
- 22
- Pages
- 4550-4562
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- PMC
- PMC3209250
- OpenAlex
- W2138329729
- Cited by
- 66
- References
- 0
- Citations by year
- 2026: 5 · 2025: 3 · 2024: 6 · 2023: 6 · 2022: 4 · 2021: 5 · 2020: 6 · 2019: 4 · 2018: 3 · 2017: 4 · 2016: 6 · 2015: 2 · 2014: 3 · 2013: 6 · 2012: 3
- FWCI
- 1.70
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Molecular and Cellular Biology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- ASEP (submittedVersion, public-domain)
- Funders
- University of Birmingham
- Universität zu Köln
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
- Keywords
- transmembrane adaptor proteins, immunological synapse, antigen-presenting cells, B cells, tetraspanin-enriched microdomains, lipid rafts, Csk, Lyn kinase, tyrosine phosphorylation, palmitoylation, T cell activation, antigen presentation, negative regulation of signaling
- MeSH terms
- CSK Tyrosine-Protein Kinase, Amino Acid Sequence, Antigen-Presenting Cells, Histocompatibility Antigens Class II, B-Lymphocytes, Humans, Lymphocyte Activation, Membrane Proteins, Molecular Sequence Data, Phosphoproteins, Protein-Tyrosine Kinases, T-Lymphocytes, Signal Transduction, Antigen Presentation, src Homology Domains, src-Family Kinases, Mitogen-Activated Protein Kinases, Membrane Microdomains, RNA Interference, RNA, Small Interfering, Adaptor Proteins, Signal Transducing, Immunological Synapses, HEK293 Cells
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