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PMID: 2419471 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

I-A-restricted T cell antigen recognition. Analysis of the roles of A alpha and A beta using DNA-mediated gene transfer.

The Journal of experimental medicine ·Vol. 163 ·No. 3 ·1986-03-01 ·Pages 678-96

Lechler RI, Ronchese F, Braunstein NS, Germain RN

Abstract

The contributions of A alpha and A beta chains, and of subregions of A beta, to Ia-restricted recognition of antigen by Th lymphocytes were analyzed using a panel of L cells transfected with various pairs of A alpha b,d, or k genes and recombinant or wild-type A beta b,d, or k genes. The A beta genes included all possible exchanges of the whole NH2-terminal (beta 1) domain or halves of the beta 1 domain among these three allelic A beta genes. The Ia+ L cells derived from such transfections were used as antigen-presenting cells with a 21 member panel of responding Ia-restricted T hybridoma cells of differing nominal antigen specificity and Ia-restriction. Special care was taken to account for quantitative variation in levels of Ia expression throughout the experiments. The results of this analysis reveal that (a) only 2 of the 21 Th cells recognized Ia molecules involving either a nonparental A alpha or a nonparental A beta chain, and in both cases the degeneracy extended to only one of the two other alleles tested. This suggests that allele specific contributions from both A alpha and A beta chains are important in restricted recognition for most, if not all I-A-restricted Th cells. (b) In no case did substitution of the A beta 2 domain from either of the alternative haplotypes lead to any functionally detectable effects, demonstrating that polymorphisms in the A beta 1 domain can entirely account for the restriction imposed on Th cell responses by the entire A beta chain. (c) For 90% of the cells tested, replacement of the NH2-terminal portion of the beta 1 domain with an allogeneic segment led to Ia molecules unable to elicit Th responses. Furthermore, of all the cells permissive of the substitution of one or other half of the beta 1 domain, only two permitted the substitution of sequence from both alternative haplotypes. Taken together, these data strongly suggest that antigen recognition by most, if not all, I-A-restricted Th cells involves contributions from both halves of the A beta 1 domain. These data suggest that the role of I-A molecules in restricted Th cell recognition of antigen depends on conformational determinants unique to a particular combination of polymorphic alpha and beta chains, and that multiple such sites exist on a single Ia molecule.(ABSTRACT TRUNCATED AT 400 WORDS)

MeSH Terms
Animals Antigen-Presenting Cells/immunology DNA/genetics DNA, Recombinant Dose-Response Relationship, Immunologic Epitopes Genes Genotype Histocompatibility Antigens Class II/immunology Hybridomas/immunology L Cells Mice Polymorphism, Genetic Receptors, Antigen, T-Cell/genetics,immunology T-Lymphocytes/immunology Transfection
Chemicals
DNA, Recombinant Epitopes Histocompatibility Antigens Class II Receptors, Antigen, T-Cell DNA
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Lechler R I
Ronchese F
Braunstein N S
Germain R N
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.163.3.678
Published
1986-03-01
Pages
678-96
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2188054
Subset
IM
External Links
PubMed source DOI: 10.1084/jem.163.3.678 PMC Full Text View journal details
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