In a clinical trial of a new antiviral vaccine composed of a recombinant viral peptide and adjuvant, 4% of the healthy recipients did not show evidence of response to the immunization. Further investigation revealed that all the nonresponders expressed the same, single allelic variant of HLA-DR but all the responders were heterozygous for HLA-DR alleles. Which of the following is the most likely explanation for this finding?
A)Response to the vaccine requires T cell recognition of complexes of the viral peptide with HLA-DR, but the peptide cannot bind to the allelic variant of HLA-DR found in the nonresponders.
B)The nonresponders could not express class II MHC proteins.
C)The viral peptide is not an immunodominant epitope.
D)The nonresponders underwent determinant selection of another viral epitope.
E)Because of technical errors, the nonresponders had not received adequate doses of the vaccine.

Question

Quizplus · Accepted Answer

The response to a viral protein (or peptide) requires T cell recognition of the peptide bound to an MHC molecule. Although the viral peptide in the vaccine may bind to many different MHC alleles, it likely will not bind to all. The nonresponders express an allelic variant of HLA-DR, which is a class II MHC molecule. Because the peptide evoked a response in 96% of the people in the trial, it can be considered a dominant epitope. Formally, this can be concluded only when the whole protein is the immunogen and the specificities of the responses for different epitopes are compared. Determinant selection is an older term that predates our knowledge of peptide-MHC binding, but it does not mean active selection for one versus another epitope. It is highly unlikely that the only people in the trial who were not adequately immunized for technical reasons happen to be the only ones homozygous for a particular MHC allele.

In a Clinical Trial of a New Antiviral Vaccine Composed