THE RECOGNITION OF CHIMERAS OF RAT AND HUMAN CD4 BY HIV-1 GP120 AND BY MONOCLONAL-ANTIBODIES

The use of chimeras of rat and human CD4 to probe the HIV-1 gp120 and antibody binding properties of CD4 is reviewed. Short segments of huma n CD4 sequence were substituted for the equivalent regions of rat CD4 which does not bind gp120, and analysis of the properties of these chi meras established: (i) that residues 33-58 of the NH2-terminal domain of human CD4 encompass the high-affinity gp120 binding site; and (ii) that chimeras containing residues 33-62 mediate HIV-1 infection. The c himera-binding specificities of gp120 and a large panel of anti-CD4 an tibodies were also determined. This allowed a critical test of the pop ular notion that receptor mimics appear at high frequency among antibo dies elicited by immunization with receptor ligands and that anti-idio typic antibodies can be used to identify novel receptors. The data sug gest that such mimics appear infrequently, if at all, a result which i s consistent with the failure of the anti-idiotype approach to identif y new genes encoding receptors with prescribed functions.