Recognition by Human Β Cells of Foreign Antigen in the Context of the MHC: a Review

Ihe expenmental evidence foi the existence of human Β cells that recognize foieign antigen in the conlexl of the MHC is very restnrted not lo say limited to only one example (Van Leeuwen et al 1979) at least with legatd to the known nature of the MHC allele and the antigen mvolved On the other hand in exenmental animal modeis, the number of antigen specific MHC restricted antibodies leported (see the detailed descnptions by different authois in this volume) greatly exceeds one though it does not reach overwhelming levels Nevertheless, the independent observations strongly support the notion that MHC lestncted antibodies do exist although with Special regard to the human studies moie data aie needed to strengthen the evidence for the existence of such antibodies in man The assumption that some Β cells aie capable of geneiatmg MHC restricted anti gen specific antibodies is based on oui earlier observation Moie than one decade has now elapsed smee participation ot the HLA molecules in the lecognition of foi eign antigen by cytotoxic T-lymphocytes (Cils) was leported (Gouimy et al 1976) Although such recognition is chaiactenstic foi Γ colls a caieful analysis of the seium of the female patient whose lymphocytes were able to demonstrate HLA A2 restricted H Υ specific cytotoxic activity levealed Β cell mediated activity compara ble with the cytotoxic Τ cell responses (Van leeuwen et al 1979) It became appai ent that lympholytic antibodies weie piesent in the serum which reacted with some mononuclear cells labend with anti Ig Ihe antibody activity was found in the IgM fraction The scrum was tested agamst a panel of iymphocytes of healthy male and female donors either positive οι negative for the lestncting molecule (i e Hl Α Α2) Ihe lesults demonstratec, that all Hl Α A2 positive male donois weie rea ting witn this antiserum whe eas the lymphocytes ol III Α Α2 negative male οι female donors were negative in the complemcnt dependent cylotoxicity assay Nevertheless of the H1A A2 positive female donois two gave a boideihne positive reaction It should be noted that ihe lymphocytes of onp of Ihe latter females weie also boideilmo lysed by the hl Α A2 lestnctod anti 11 Υ C ILs in the CV1I assay Comparalive analysis between thr outcome of the CM1 assav and the icactions obtained with the anti seium showed striking similanty (lable I) Because of the almost peifect correlation between the reactivity patterns of the CIIs and the anlibody it is ifasonable to assume that the HLA A2 testiicted antibody tecogni/es the same epitopes on the III Λ Α2 and on the 11 \ anligen as do ihe III Λ Α2 lestucted CIIs obtained fiom the same individual Since vanants exist both at the level ol the anligen c η Anti