Monday, April 11, 2005

438: STRUCTURAL BIOLOGY: "D" Is Not for Diversity -- Garboczi 308 (5719): 209 -- Science

STRUCTURAL BIOLOGY: "D" Is Not for Diversity -- Garboczi 308 (5719): 209 -- Science:

our structural understanding of γδ TCRs is limited because, until now, the only structures available have been those of a Vδ domain from a human γδ TCR (4) and a γδ TCR expressed by human γδ T cells in the bloodstream (5). These structures reveal the domains of γδ TCRs and a putative antigen-binding site, but not how a γδ TCR binds to its antigen. Unlike antibodies and αβ TCRs, γδ TCRs have few known ligands. For a molecular understanding of γδ T cell function, we need to know the antigens that γδ TCRs bind and how they are recognized. This requires determining the structure of a γδ TCR in a complex with its antigen. The best-known antigens for mouse γδ TCRs are the nonclassical MHC proteins known as T10 and its close relative T22 (6). Now, Shin et al. (2) demonstrate that there is a substantial population of mouse γδ T cells bearing surface TCRs that carry a full-length D gene segment (Dδ2) and bind to the T22 molecule. In a complementary study, Adams et al. (3) determine the crystal structure of a γδTCR/T22 complex. Their structure reveals how G8, one of the γδ TCRs studied by Shin et al., binds to the T22 molecule--G8 uses amino acid residues encoded by the Dδ2 gene.

Unlike αβ TCRs that recognize and bind to antigenic peptides complexed with MHC molecules, γδ TCRs do not recognize peptides. In fact, their recognition of T22 molecules does not depend on the cellular antigen-processing machinery that generates antigenic peptides.
I'm confident that that text is all in english. It relates to the evolution and structure of the immune system in humans and mice. Common descent, evolutionary hypotheses, etc.