Impact of HLA-B Alleles, Epitope Binding Affinity, Functional Avidity, and Viral Coinfection on the Immunodominance of Virus-Specific CTL Responses

Florian Bihl, Nicole Frahm, Loriana Di Giammarino, John Sidney, Mina John, Karina Yusim, Tonia Woodberry, Kaori Sango, Hannah S. Hewitt, Leah Henry, Caitlyn H. Linde, John V. Chisholm III, Tauheed M. Zaman, Eunice Pae, Simon Mallal, Bruce D. Walker, Alessandro Sette, Bette T. Korber, David Heckerman and Christian Brander
J Immunol April 1, 2006, 176 (7) 4094-4101; DOI: https://doi.org/10.4049/jimmunol.176.7.4094

Article Figures & Data

Figures

  • FIGURE 1.
    FIGURE 1.

    HLA-A-, HLA-B-, and HLA-C-restricted CTL epitopes differ in the frequency of recognition and magnitude of responses: Previously defined epitopes in HIV and EBV were tested in 98 and 91 subjects, respectively, and epitope-specific frequency of recognition among individuals expressing the described HLA allele was determined for HLA-A-, HLA-B-, and HLA-C-restricted epitopes derived from HIV (A) and EBV (B). The median magnitude of responses was calculated for all epitopes targeted at least once in the cohort and compared among HLA-A-, HLA-B-, and HLA-C-restricted epitopes and between HIV (C) and EBV (D) epitopes. Mann-Whitney U analysis was performed to compare epitopes restricted by the different loci.

  • FIGURE 2.
    FIGURE 2.

    Correlation between magnitude of responses and frequency of recognition: The frequency of epitope recognition among individuals expressing the described, restricting HLA allele and the median magnitude of responses among the epitope responders were compared for HIV epitopes (a), EBV (b) epitopes and for both viruses together (c). Spearman correlations were performed using adjusted allele frequencies as described in Materials and Methods.

  • FIGURE 3.
    FIGURE 3.

    Epitope binding does not correlate with magnitude of response or frequency of recognition: Epitope binding affinities for 87 HIV epitopes and 48 EBV-derived epitopes were compared with frequency of recognition (A and B) or the median magnitude of response (C and D). Spearman correlations were performed using adjusted allele frequencies as described in Materials and Methods.

  • FIGURE 4.
    FIGURE 4.

    Functional avidity, but not HLA binding, is associated with magnitude of recognition: The functional avidity, defined as the peptide concentration required to achieve half-maximal reactivity (SFC/106 PBMC) in ELISPOT assays was determined for 46 different HIV epitopes, partially tested multiple times as indicated in the table (left). Functional avidities in HLA-A-, HLA-B-, and HLA-C-restricted epitopes were compared among each other (A), to epitope binding affinities (B), or to magnitude of responses (C). A–C contain all 70 data points, whereas the table reflects median magnitudes and SD50 in cases where multiple individuals were tested for the same epitope.

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