Alloantiserum induced blockade of Ir gene product function

ABSTRACT The activation of guinea pig thymus derived lymphocytes by antigens, the response to which is controlled by histocompatibility–linked immune response (Ir) genes, may be specifically blocked by alloantisera prepared by reciprocal immunization of strain 2 and strain 13 guinea pigs. This blockade is specific in that anti-2 serum blocks the response of (2 × 13)F1 cells to antigens responsiveness to which is controlled by 2-linked Ir genes while anti-13 serum blocks response dependent on 13-linked Ir genes. The inhibitory antibodies appear to be directed at antigens specified at the 2/13 locus rather than at the Ir gene products themselves. Anti-2 serum blocks responses to the copolymer of glutamic acid and alanine (GA) of cells from 2+GA+ animals but not of cells from 2-GA+ animals. Studies of the 2 alloantigen indicate a molecular weight of ~25,000 Daltons, absence of a low molecular weight polypeptide chain and an expression principally on lymphocytes. We suggest a model in which the Ir gene product exists as a molecular complex with the 2/13 histocompatibility antigen. In this model, the Ir gene product is responsible for the specific recognition functions of the complex and the alloantigens mediate biologic functions, such as histocompatibility dependent cellular interactions.