Inhibition of antigen-specific T lymphocyte activation by structurally related Ir gene-controlled polymers. II. Competitive inhibition of I-E-restricted, antigen-specific T cell responses.

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Abstract
A highly specific competitive inhibition exists between a pair of structurally related antigens (GT [L-glutamic acid-50-L-tyrosine-50] and GAT [L-glutamic acid-60-L-alanine-30-L-tyrosine-10]) for antigen presentation by [mouse] accessory cells. This phenomenon was investigated in a 2nd antigenic system, which is controlled by a distinct Ir [immune reponse] gene product. Two GL.vphi. [L-glutamic acid-56-L-lysine-35-L-phenylalanine-9]-specific, I-Ed-restricted, interleukin 2-producing T cell hybridomas were constructed. The antigenic fine specificity of these 2 hybrid clones was distinct. One hybrid reacted solely with GL.vphi. while the 2nd cross-reacted with GLleu [L-glutamic acid-55-L-lysine-35-L-leucine-10] and GLT [L-glutamic acid-55-L-lysine-35-L-tyrosine-10]. These latter 2 copolymers, as well as the antigen GL, inhibited the GL.vphi. response of the non-cross-reactive hybrid. The structurally related antigen G.vphi. [L-glutamic acid-62-L-phenylalanine-38] was not inhibitory for this clone''s response. The cross-reactive GL.vphi. hybrid could also be inhibited, but, in this case, G.vphi. and not GL [L-glutamic acid-60-L-lysine-40] caused the inhibition. Reciprocal inhibitions could be demonstrated between these and other hybrids (e.g., GAT responsive), indicating a very high degree of specificity to the inhibition. The inhibition caused by the various copolymers was reversible by increasing the concentration of GL.vphi.. This effect was localized to the antigen-presenting cell and not the T cell hybridoma. Functionally, this competition did not appear to be for antigen uptake or general antigen processing. The findings generalize the phenomenon of antigen competition to a 2nd antigen system in the context of a 2nd Ia molecule. The possible mechanisms accounting for the complex pattern of specificities in this system are discussed.

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