T-cell recognition of Ia molecules selectively altered by a single amino acid substitution.
T lymphocytes recognize foreign antigen together with allele-specific determinants on membrane-bound class I and class II ( Ia) gene products of the major histocompatibility complex. To identify amino acids of class II molecules critical to this recognition process, the genes encoding the beta chains of the I-Ak molecule were cloned from a wild-type B-cell hybridoma and from an immunoselected variant subline showing distinct serological and T-cell stimulatory properties. Nucleotide sequencing and DNA-mediated gene transfer established that a single base transition (G----A) encoding a change from glutamic acid to lysine at position 67 in the I-Ak beta molecule accounted for all the observed phenotypic changes of the variant cells. These results confirm the importance of residues 62 to 78 in the amino terminal domain of I-A beta for class II-restricted T-cell recognition of antigen and demonstrate the ability of a single substitution in this region to alter this recognition event.[1]References
- T-cell recognition of Ia molecules selectively altered by a single amino acid substitution. Brown, M.A., Glimcher, L.A., Nielsen, E.A., Paul, W.E., Germain, R.N. Science (1986) [Pubmed]
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