Coevolution of TCR-MHC interactions: Conserved MHC tertiary structure is not sufficient for interactions with the TCR Journal Article

   


Authors: Kim, H. J.; Guo, D.; Sant'angelo, D. B.
Article Title: Coevolution of TCR-MHC interactions: Conserved MHC tertiary structure is not sufficient for interactions with the TCR
Abstract: The specificity for self-MHC that is necessary for T cell function is a consequence of intrathymic selection during which T cell antigen receptors (TCRs) expressed by immature thymocytes are tested for their affinity for self-peptide:self-MHC. The germ-line-encoded segments of the TCR, however, are believed to have an innate specificity for structural features of MHC molecules. We directly tested this hypothesis by generating a transgenic mouse system in which the protein HLA-DM is expressed at the surface of thymic cortical epithelial cells in the absence of classical MHC molecules. The specialized intracellular function of HLA-DM has removed this MHC class II-like protein from the evolutionary forces that have been hypothesized to shape TCR-MHC interactions. Our study shows that a structural mimic of MHC class II is not sufficient to appropriately interact with the TCRs expressed by developing thymocytes. This result emphasizes the unique complementarity of TCR-MHC interactions that are maintained by the evolutionary pressures dictated by positive selection. © 2005 by The National Academy of Sciences of the USA.
Keywords: immunohistochemistry; protein expression; nonhuman; flow cytometry; binding affinity; protein function; t lymphocyte; animal cell; mouse; animals; mice; cells, cultured; cell function; cell maturation; protein interaction; transfection; cell specificity; transgenic mouse; mus musculus; mice, transgenic; evolution, molecular; t lymphocyte receptor; thymus; receptors, antigen, t-cell; thymus gland; major histocompatibility antigen class 2; epithelium cell; protein structure, tertiary; major histocompatibility complex; stroma cell; hla dm antigen; hla-d antigens; thymocyte; protein tertiary structure; t lymphocytes; dna, complementary; endosome; t lymphocyte antigen; t cell receptor; thymocytes
Journal Title: Proceedings of the National Academy of Sciences of the United States of America
Volume: 102
Issue: 20
ISSN: 0027-8424
Publisher: National Academy of Sciences  
Date Published: 2005-05-17
Start Page: 7263
End Page: 7267
Language: English
DOI: 10.1073/pnas.0502751102
PUBMED: 15883386
PROVIDER: scopus
PMCID: PMC1091755
DOI/URL:

http://www.scopus.com/inward/record.url?eid=2-s2.0-18844365885&partnerID=40&md5=7a6f22ad7190665f5c991bc7e077dbcb
Notes: --- - "Cited By (since 1996): 7" - "Export Date: 24 October 2012" - "CODEN: PNASA" - "Source: Scopus"
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MSK Authors
  1. Hye-Jung Kim
    5 Kim
  2. Derek B Sant'angelo
    46 Sant'angelo
  3. Donglin Guo
    4 Guo
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