|
pubmed:abstractText |
The ?? T cell receptor (TCR) differs from immunoglobulin and ?? TCR in its overall binding mode. In human, genes ?1, ?2, and ?3 are used for TCR? chains. Previously, we have studied antigen binding determinants of TCR?2 derived from dominant ?? T cells residing in peripheral blood. In this study we have investigated the critical determinants for antigen recognition and TCR function in TCR?1 originated from gastric tumor-infiltrating ?? T lymphocytes using three independent experimental strategies including complementary determining region 3 (CDR3) of TCR?1 (CDR3?1)-peptide mediated binding, CDR3?1-grafted TCR fusion protein-mediated binding, and TCR?4?1- and mutant-expressing cell-mediated binding. All three approaches consistently showed that the conserved flanking V and J sequences but not the diverse D segment in CDR3?1 determine the antigen binding. Most importantly, we found that mutations in the V and J regions of CDR3?1 also abolish the assembly of TCR and TCR-CD3 complexes in TCR?4?1-transduced J.RT3-T3.5 cells. Together with our previous studies on CDR3?2 binding, our finding suggests that both human TCR?1 and TCR?2 recognize antigen predominately via flanking V and J regions. These results indicate that TCR?? recognizes antigens using conserved parts in their CDR3, which provides an explanation for a diverse repertoire of ??TCRs only recognizing a limited number of antigens.
|
|
pubmed:affiliation |
Department of Immunology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, National Key Laboratory of Medical Molecular Biology, Beijing 100005, China.
|
