We determined the MHC restriction of CTL responses to five individual influenza virus proteins. Four viral proteins failed to be recognized in conjunction with three of the five class I alleles of the H-2k and H-2d haplotypes, while the fifth was recognized only in conjunction with a single allele. This indicates that there is a significant chance that a given class I allele will be associated with low responsiveness or nonresponsiveness for a given foreign protein. This explains, at least in part, why MHC-linked nonresponsiveness is frequently detected in polyclonal antiviral CTL responses. Most importantly, these findings support the idea that responsiveness to foreign antigens is a critical factor in maintaining the high degree of MHC class I polymorphism in outbred populations.

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