Abstract
Class I major histocompatibility complex (MHC) restricted T lymphocytes preferentially recognize fragments of polypeptides processed through a nonendosomal presentation pathway. At present the intracellular compartment(s) in which polypeptide fragmentation occurs and factors which influence the formation of an antigenic epitope are not well understood. To assess the role of residues flanking an antigenic site in the generation of the antigenic moiety recognized by class I MHC restricted T lymphocytes we have moved the coding sequence for an immunodominant H-2Kd restricted site on the influenza A/JAPAN/57 hemagglutinin (residues 202-221) by site-directed mutagenesis to six different positions along the coding sequence of the hemagglutinin gene. We have found that all six classes of mutants are recognized by MHC class I restricted T cells as efficiently as the wild type hemagglutinin gene product. Thus neither N-terminal to C-terminal position within the translation product nor sequences flanking the antigenic site influence processing.
MeSH Terms
Amino Acid Sequence
Animals
Antigens, Viral/genetics,immunology
Base Sequence
DNA Mutational Analysis
H-2 Antigens/immunology
Hemagglutinins, Viral/genetics,immunology,metabolism
In Vitro Techniques
Mice
Molecular Sequence Data
Peptides/immunology
Recombinant Proteins/immunology
Structure-Activity Relationship
T-Lymphocytes, Cytotoxic/immunology
Chemicals
Antigens, Viral
H-2 Antigens
Hemagglutinins, Viral
Peptides
Recombinant Proteins
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Hahn Y S
Department of Pathology, Washington University School of Medicine, St. Louis, Missouri 63110.
Braciale V L
Braciale T J
References (16)
16 references, click to expand
-
Cytotoxic T lymphocytes recognize influenza haemagglutinin that lacks a signal sequence.
Nature. 1986 Dec 11-17;324(6097):575-7
PMID: 3491325
-
The recognition of a viral antigenic moiety by class I MHC-restricted cytolytic T lymphocytes is limited by the availability of the endogenously processed antigen.
J Immunol. 1990 Nov 15;145(10):3188-93
PMID: 1700000
-
Class I major histocompatibility complex-restricted T lymphocyte recognition of the influenza hemagglutinin. Overlap between class I cytotoxic T lymphocytes and antibody sites.
J Exp Med. 1989 Oct 1;170(4):1357-68
PMID: 2477491
-
Recognition of pre-processed endogenous antigen by class I but not class II MHC-restricted T cells.
Nature. 1989 Nov 9;342(6246):180-2
PMID: 2478887
-
Class I MHC-restricted recognition of cells expressing a gene encoding a 41 amino acid product of the influenza hemagglutinin.
J Immunol. 1988 Nov 15;141(10):3324-8
PMID: 2460530
-
Influences of antigen processing on the expression of the T cell repertoire. Evidence for MHC-specific hindering structures on the products of processing.
J Exp Med. 1988 Jul 1;168(1):357-73
PMID: 2456373
-
On the role of the transmembrane anchor sequence of influenza hemagglutinin in target cell recognition by class I MHC-restricted, hemagglutinin-specific cytolytic T lymphocytes.
J Exp Med. 1987 Sep 1;166(3):678-92
PMID: 2442285
-
The epitopes of influenza nucleoprotein recognized by cytotoxic T lymphocytes can be defined with short synthetic peptides.
Cell. 1986 Mar 28;44(6):959-68
PMID: 2420472
-
Class I cross-restricted T cells reveal low responder allele due to processing of viral antigen.
Nature. 1989 Feb 16;337(6208):653-5
PMID: 2537466
-
Introduction of soluble protein into the class I pathway of antigen processing and presentation.
Cell. 1988 Sep 9;54(6):777-85
PMID: 3261634
-
Oligonucleotide-directed mutagenesis: a simple method using two oligonucleotide primers and a single-stranded DNA template.
DNA. 1984 Dec;3(6):479-88
PMID: 6096101
-
Differences in antigen presentation to MHC class I-and class II-restricted influenza virus-specific cytolytic T lymphocyte clones.
J Exp Med. 1986 Apr 1;163(4):903-21
PMID: 3485173
-
Assembly of MHC class I molecules analyzed in vitro.
Cell. 1990 Jul 27;62(2):285-95
PMID: 2196996
-
Heterogeneity and specificity of cloned lines of influenza-virus specific cytotoxic T lymphocytes.
J Exp Med. 1981 Apr 1;153(4):910-23
PMID: 6166708
-
Transport protein genes in the murine MHC: possible implications for antigen processing.
Science. 1990 Dec 21;250(4988):1723-6
PMID: 2270487
-
Cytotoxic T cells recognize fragments of the influenza nucleoprotein.
Cell. 1985 Sep;42(2):457-67
PMID: 2411422