N-LINKED GLYCANS IN THE CD4-BINDING DOMAIN OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 ENVELOPE GLYCOPROTEIN GP160 ARE ESSENTIAL FOR THE IN-VIVOPRIMING OF T-CELLS RECOGNIZING AN EPITOPE LOCATED IN THEIR VICINITY

Deglycosylation of viral glycoproteins has been suggested to influence the number of available T cell determinants and to increase T cell re cognition of antigens. In this study, we have investigated whether T c ell responses to the HIV-I envelope glycoprotein gp160 were influenced by deletion of three N-glycans of the protein. Wild type (wt) and a m utated form of gp160 (gp160(A123)) lacking the three N-glycans in the C-terminal CD4-binding region efficiently induced antigen-specific T c ell responses in mice of the H-2(b), H-2(d), and H-2(k) haplotypes. Fu rther, T cells primed by either wt gp160 or gp160(A123) were stimulate d in vitro to a similar extent by the homologous and heterologous prot ein, indicating that deletion of the glycans did not affect the overal l immunogenicity and antigenicity of gp160(A123). Wild-type gp160 and gp160(A123) induced comparable T cell responses to those of epitopes w hich with respect to the secondary structure of gp160 were distant fro m the deleted glycans. However, in mice of the H-2(b) haplotype, wt gp 160 primed T cells which responded in vitro to a peptide containing on e of the deleted N-glycosylation sites (Asn(448)), whereas T cells ind uced by gp160(A123) were unable to recognize this peptide. Thus, delet ion of the glycans abrogated the in vivo priming of T cells recognizin g an epitope in close proximity to the deletion sites. Furthermore, en zymatically deglycosylated gp160 failed to induce a T cell response to this epitope. These results indicate that the in vivo generation of c ertain T cell determinants from glycoproteins is dependent on the glyc osylation of the protein. (C) 1996 Academic Press, Inc.