Your browser version may not work well with NCBI's Web applications. More information here...
1: Proc Natl Acad Sci U S A. 2005 May 17;102(20):7263-7. Epub 2005 May 9.
Related Articles, Links
Click here to read Click here to read Click here to read
Coevolution of TCR-MHC interactions: conserved MHC tertiary structure is not sufficient for interactions with the TCR.

Kim HJ, Guo D, Sant'Angelo DB.

Laboratory of T Cell Immunobiology, Immunology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.

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.

Publication Types:
PMID: 15883386 [PubMed - indexed for MEDLINE]

PMCID: PMC1091755