IMMUNE RESPONSIVENESS IN MUTANT MICE LACKING T-CELL RECEPTOR ALPHA-BETA(+) CELLS

Immune responses of mice with T-cell receptor (TCR)gamma delta(+) T ce lls but lacking TCR alpha beta(+) cells because of a disruption in the TCR alpha gene, were analysed against alloantigens, soluble protein a ntigen, killed Mycobacterium tuberculosis and exogenous superantigen. Rejection of skin allografts mismatched for classical major histocompa tibility complex (MHC) plus multiple minor H antigens was virtually ab rogated but the presence of mismatched Qa-1 non-classical MHC antigens on donor tissue resulted in a significant proportion of TCR alpha(-/- ) mice rejecting such grafts. In view of the proposed role for gamma d elta T cells in mycobacterial responses, and particularly against self - or mycobacterial heat-shock protein HSP 65, we examined these respon ses in TCR alpha(-/-) mice. Local responses after immunization were lo w in lymph nodes and no component of these was directed against mycoba cterial HSP 65. However, splenic T cells from mutant mice responded st rongly to either purified protein derivative (PPD) or M. tuberculosis. Our findings indicate that TCR alpha(-/-) mice are selectively compro mised: while responses to (undefined) mycobacterial antigens were subs tantial, responses to some other target antigens such as MHC alloantig ens and HSP 65, believed to be preferentially recognized by gamma delt a receptors, were poor or absent. However, the fact that the mutant mi ce more readily rejected allografts, that are mismatched for the non-c lassical MHC antigen Qa-1 in addition to classical MHC and minor-H inc ompatibility, indicates that in some mice the residual immune response , presumed to be by gamma delta cells, is sufficient to cause skin gra ft rejection and that recognition of non-classical MHC antigens may pl ay an important part in the response.