Major histocompatibility complex binding and T cell recognition of a viral nonapeptide containing a minimal tetrapeptide.
The primary immune response of cytotoxic T lymphocytes in H-2d and H-2q mice to infection with lymphocytic choriomeningitis virus is directed mostly towards the common major T cell epitope of amino acids 112-132 on the viral nucleoprotein (NP). The molecules responsible for presentation of the T cell epitope NP112-132 are in both haplotypes the MHC class I L antigens (Ld, Lq). Truncations of the amino and carboxy termini of the NP 112-132 sequence revealed the nonapeptide RPQASGVYM (NP118-126) as a most effective peptide antigen, but even the tetrapeptide GVYM was recognized by CTL of both haplotypes in a class I antigen-restricted specificity. When tyrosine (Y) or methionine (M) were substituted with alanine, CTL recognition of the altered nonamer required 10(6) to 10(8) times higher peptide concentrations and in one case (Y----A on Ld) the peptide was not recognized at all. Up-modulation of the expression of Ld and Lq class I antigens as measured by flow cytometry correlated with the ability to present the peptide antigens. The only exception was peptide NP118-126 (M----A), which was recognized by T cells on L-Ld and L-Lq target cells but failed to up-regulate Ld and Lq antigens.
Schulz
M
M
Department of Experimental Pathology, University Hospital, Zürich, Switzerland.
Aichele
P
P
Schneider
R
R
Hansen
T H
TH
Zinkernagel
R M
RM
Hengartner
H
H
D000595:Amino Acid Sequence; D000818:Animals; D000939:Epitopes / Q000032:analysis; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D008217:Lymphocytic choriomeningitis virus; D051379:Mice; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000276:immunology*; D013329:Structure-Activity Relationship; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014764:Viral Proteins / Q000276:immunology*
D000939:Epitopes; D015395:Histocompatibility Antigens Class I; D009842:Oligopeptides; D014764:Viral Proteins