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- Title
High Peptide Affinity for MHC Class I does not Correlate with Immunodominance.
- Authors
Müllbacher; Lobigs; Yewdell; Bennink; Tha Hla; Blanden
- Abstract
Cytotoxic T (Tc)-cell responses against influenza virus infection in BALB/c (H-2[sup d]) mice are dominated by Tc clones reactive to the viral nucleoprotein (NP). Here, we report investigations using recombinant vaccinia viruses (VV) encoding major histocompatibility complex (MHC) class I H-2K[sup d] molecules differing by a single amino acid from glutamine (wild-type, K[sup dw]) to histidine (mutant, K[sup dm]) at position 114 located in the floor of the peptide-binding groove. Influenza-infected target cells expressing K[sup dw] were strongly lysed by K[sup d]-restricted Tc cells against A/WSN influenza virus or the immunodominant peptide of viral NP (NPP[sup 147–155]), whereas infected K[sup dm]-expressing targets gave little or no lysis, respectively, thus showing the immunodominance of NPP[sup 147–155]. K[sup dm]-expressing target cells saturated with synthetic NPP[sup 147–155] (10[sup -5] m) were lysed similarly to K[sup dw]-expressing targets by NPP[sup 147–155]-specific Tc cells. Thus the defect in influenza-infected K[sup dm]-expressing targets was quantitative; insufficient K[sup dm]–peptide complexes were expressed. Tc-cell responses against four other viruses or alloantigens showed no effect of K[sup dm]. When peptide transport-defective cells were infected with VV-K[sup dw] or VV-K[sup dm] and co-infected with a recombinant VV encoding an endoplasmic reticulum-targeted viral peptide, two influenza haemaglutinin peptides caused higher expression of K[sup dw] than NPP[sup 147–155] indicating their higher affinity for K[sup dw]. These results are inconsistent with the hypothesis that immunodominance in the anti-influenza response reflects high affinity of the immunodominant peptide, but are consistent with skewing of the Tc-cell receptor repertoire.
- Subjects
PEPTIDE receptors; MAJOR histocompatibility complex; VACCINIA
- Publication
Scandinavian Journal of Immunology, 1999, Vol 50, Issue 4
- ISSN
0300-9475
- Publication type
Article