A five-residue HIV envelope helper T cell determinant: does this peptide-MHC interaction leave the binding groove half empty?
High-resolution structures have revealed major pockets in the MHC class II peptide binding groove within a region designated Pl-P9. The region can accommodate 9-mer peptides, consistent with the observation that minimal core helper T (Th) cell determinants are usually eight or nine residues in size. Here we describe mouse Th cell hybridomas that are specific for a core peptide of only five residues (NPIIL) in the HIV envelope glycoprotein. Effective Th cell stimulation requires that these MHC class II Ia(b)-presented peptides contain amino acids flanking the minimal pentamer, but the flanking residues may be located on either the N or C terminus. To explain these findings, we suggest that mini-Th cell epitopes may effectively associate with MHC when only five (or possibly fewer) of the P1-P9 positions are filled. The remaining positions may be empty, or may be associated with a second, perhaps unrelated, peptide moiety.
Lockey
Timothy D
TD
Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.
Surman
Sherri
S
Brown
Scott
S
Slobod
Karen S
KS
Coleclough
Christopher
C
Doherty
Peter C
PC
Hurwitz
Julia L
JL
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D015686:Gene Products, env / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism; D015497:HIV-1 / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D006825:Hybridomas; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
D018984:Epitopes, T-Lymphocyte; D015686:Gene Products, env; D000949:Histocompatibility Antigens Class II; D010455:Peptides