ISOLATION AND CHARACTERIZATION OF MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-IIB GENES FROM THE NURSE SHARK

The major histocompatibility complex (MHC) contains a set of linked ge nes which encode cell surface proteins involved in the binding of smal l peptide antigens for their subsequent recognition by T lymphocytes. MHC proteins share structural features and the presence and location o f polymorphic residues which play a role in the binding of antigens. I n order to compare the structure of these molecules and gain insights into their evolution, we have isolated two MHC class IIB genes from th e nurse shark, Ginglymostoma cirratum. Two clones, most probably allel es, encode proteins which differ by 13 amino acids located in the puta tive antigen-binding cleft. The protein structure and the location of polymorphic residues are similar to their mammalian counterparts. Alth ough these genes appear to encode a typical MHC protein, no T-cell-med iated responses have been demonstrated in cartilaginous fish. The nurs e shark represents the most phylogenetically primitive organism in whi ch both class IIA [Kasahara, M., Vazquez, M., Sato, K., McKinney, E. C . & Flajnik, M. F. (1992) Proc. Natl. Acad. Sci USA 89, 6688-6692] and class IIB genes, presumably encoding the alpha/beta heterodimer, have been isolated.