A Possible Basis for Major Histocompatibility Complex-Restricted T-Cell Recognition
Abstract
Four distinct T-cell antigen-receptor gene loci have now been identified and partly characterized: ɑ, β, y and δ. All of these loci can rearrange in an immunoglobulin- like fashion and express polypeptides that contribute to either ɑ:β or y:δ T-cell receptor-CD3 complexes. Surprisingly, the T-cell receptor (TCR) δ coding regions are located entirely, or almost entirely, within the TCR ɑ locus and share at least some of the V region gene segments, thus at least partly linking the two different types of receptor heterodimers. Analysis of potential T-cell receptor diversity, particularly that of the δ chain, indicates a striking concentration of somatic polymorphism in the V-J junctional region of the two heterodimers, four to six orders of magnitude higher than similar calculations for immunoglobulin light- and heavy-chain combinations. In contrast, the number of possible V region combinations in T-cell receptors is one hundredth to one thousandth that of immunoglobulins. TCR ɑ:β heterodimers are known to recognize many possible fragments of antigens embedded in the peptide- binding clefts of a relatively small number of major histocompatibility complex (MHC) molecules. Thus it is attractive to speculate that the V-J junctional portions of both types of T-cell receptor contact peptide antigens, whereas the remaining diversity regions contact the MHC. This contention is supported by molecular modelling studies and has interesting implications for the evolution of antigen-receptor genes.
Additional Information
© 1989 Royal Society of London. M. M. D. is a scholar of the PEW Foundation, P.J. B. is a Postdoctoral Fellow of the American Cancer Society and J. F. E. is a Centennial Fellow of the Medical Research Council of Canada. We thank the NIH and Howard Hughes Medical Institute for grant support.Additional details
- Eprint ID
- 75806
- DOI
- 10.1098/rstb.1989.0030
- Resolver ID
- CaltechAUTHORS:20170406-111844901
- Pew Charitable Trust
- NIH
- Howard Hughes Medical Institute (HHMI)
- American Cancer Society
- Medical Research Council of Canada
- Created
-
2017-04-06Created from EPrint's datestamp field
- Updated
-
2021-11-15Created from EPrint's last_modified field