Both H-2- and non-H-2-linked genes influence influenza nucleoprotein epitope recognition by CD4+ T cells.
The specificity of the influenza nucleoprotein-induced T-cell proliferative response by mouse strains differing in either H-2- or non-H-2-linked background genes was compared by using a panel of synthetic peptides covering 90% of the nucleoprotein molecule. The results showed, as expected, that H-2 genes strongly influenced the major regions of the molecules recognized by T cells, as the response was focused on different peptides in mice of different H-2 haplotypes. However, some regions of the molecule (e.g. 260-283) were recognized by several different haplotypes, with overlapping but distinct minimal determinants. The lymph node proliferative response appeared to be predominantly restricted by the I-A molecule, as expression of I-E in mice did not result in any detectable recognition of additional epitopes. In the majority of cases the same T-cell epitopes were recognized by mouse strains sharing the same H-2 haplotype but differing in many background genes. Low responsiveness was however observed to p55-77 by DBA/2 and p127-141 by AKR mice to which other H-2d or H-2k strains were high responders. Low responsiveness is therefore unlikely to be a consequence of failure of these peptides to bind to the relevant major histocompatibility complex class II molecule. In addition antigen-presenting cells from the DBA/2 low responder strain was able to process and present whole influenza virus or nucleoprotein as well as antigen-presenting cells from the high responder BALB/c strain. It is therefore suggested that low responsiveness to the peptide p55-77 may be due to a 'hole in the T-cell repertoire', caused perhaps by expression of Mls-1a in the DBA/2 strain. This is supported by the observation that low responsiveness to this epitope appears to be dominant in F1 (low x high) mice.
Brett
S J
SJ
Molecular Immunology Group, Wellcome Research Laboratories, Beckenham, Kent, UK.
Tite
J P
JP
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D000956:Antigens, Viral / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018929:Cell Culture Techniques; D002455:Cell Division / Q000276:immunology; D000939:Epitopes / Q000276:immunology; D005260:Female; D005802:Genes, MHC Class II / Q000276:immunology*; D006183:H-2 Antigens / Q000235:genetics*; D000949:Histocompatibility Antigens Class II / Q000235:genetics; D009980:Influenza A virus / Q000276:immunology*; D051379:Mice; D008815:Mice, Inbred Strains; D009154:Mutation; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology; D016601:RNA-Binding Proteins; D014758:Viral Core Proteins / Q000276:immunology*
D000956:Antigens, Viral; D000939:Epitopes; D006183:H-2 Antigens; D000949:Histocompatibility Antigens Class II; C048842:NP protein, Influenza A virus; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins; D010446:Peptide Fragments; D016601:RNA-Binding Proteins; D014758:Viral Core Proteins