Different MHC class I alleles compete for presentation of overlapping viral epitopes

Abstract

We previously identified an HLA-B8+ donor, NW, whose lymphoblastoid cells failed to present a B8-restricted epitope from the influenza A nucleoprotein following viral infection, although added peptide could still be presented. The failure to present through HLA-B8 following viral infection appears to be specific for the NP epitope. Here, we report that donor NW makes an HLA-B2702-restricted influenza-specific CTL response to an epitope in the nucleoprotein that overlaps the B8-restricted epitope by 8 aa. Two mechanisms for the failure of this cell line to present the B8-restricted epitope following viral infection are investigated. One is that there is an antigen processing polymorphism specific to the NW cell line, so that there is either preferential generation or preferential transport of the B2702 epitope. The other is that B8 and B2702 compete for a common peptide fragment in the ER and this leads to suboptimal loading of HLA-B8.

Activation of epitope-specific memory cytotoxic T lymphocyte responses by synthetic peptides

“…Conceivably, the relatively low frequency of IVT-specific precursors may reflect a poor presentation of the epitope in cells infected by the endogenous EBV strain. This could be due to mutations affecting the processing of EBNA4 [44], or to competition for binding to IVT-precursor peptides by other HLA alleles expressed in this donor, as reported recently by Tussey et al [45].…”

Compartmentalized MHC class I antigen processing enhances immunosurveillance by circumventing the law of mass action

“…The direct association of class I molecules with the TAP-loading complex (25) provides a ready explanation for the noncompetitive behavior of ER-delivered peptides if class I molecules are positioned to selectively bind peptides transported by their cognate transporter, as seems likely. The report of Tussey et al (26) of competition between different human class I allomorphs for presentation of a peptide derived from a full-length rVV-encoded gene product is consistent with the presence of multiple class I molecules for each loading complex (27), although a recent report concluded that a single class I molecule occupies the loading complex (28).…”

“…We could identify three of the peptides in antigenic active fractions as B8R [20][21][22][23][24][25][26][27] (8) Time ( coelution with their respective synthetic peptides and their positions in the immunodominance hierarchy, which matched the respective positions of the corresponding defined peptides (12). Importantly, expression of the K b -binding peptides RGY or SIIN did not reproducibly decrease the antigenic activities of the three defined K b -restricted peptides (black arrows) or four other undefined peptides (red arrows), when peptides were tested directly from fractions, or over a 625-fold range to reach background levels of observed with fractions from uninfected cells.…”

Recognition of chlamydial antigen by HLA‐B27‐restricted cytotoxic T cells in HLA‐B*2705 transgenic CBA (H‐2k) mice

“…Recently, competition between co-expressed HLA antigens for the same peptide has been reported (46). Therefore, the lower inhibitory effect of the murine Kk MAb on J26P2-B*2705 targets could be due to competition between co-expressed HLA-B27 and H-2Kk molecules for peptides, which have higher affinity for HLA-B27.…”