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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1985 Oct;82(20):7058–7062. doi: 10.1073/pnas.82.20.7058

The murine bm12 gene conversion provides evidence that T cells recognize predominantly Ia conformation.

H Y Tse, S Kanamori, W D Walsh, T H Hansen
PMCID: PMC391309  PMID: 3931082

Abstract

The structure of the highly polymorphic Ia dimer is the genetically determined factor that controls the immune response to foreign antigens, albeit the mechanism remains unresolved. However, it is clear that, in diverse immune responses, effector T lymphocytes require recognition of self-Ia and foreign antigenic determinants on the surface of an antigen-presenting cell or an antibody-secreting B cell. Furthermore, a single Ia molecule has been found to possess several independently acting functional domains. In this report T-cell recognition of Ia was limited to a single, defined structure by using the Ia mutant mouse strain B6.C-H-2bm12 (bm12). The Ia determinant being recognized is the site of the mutation that represents a difference in three of five amino acid residues in a hypervariable region of its beta chain. This mutation has been proposed to have resulted from a gene conversion-like event and is known to have functional importance. Recognition of the bm12 mutation site was studied here in in vitro cultures of T cells generated against Iabm12 antigens. The specificity of these alloreactive T cells was tested by using stimulator cells expressing various Ia alloantigens of known structure. Our findings provide direct genetic evidence that T cells recognize predominantly conformational determinants on Ia molecules and not their primary structure. The implications of these findings on our understanding of the genetic control of the immune response and the potential to modulate these responses in an antigen-specific way are discussed.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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