The α3 domain of major histocompatibility complex class I molecules plays a critical role in cytotoxic T lymphocyte stimulation

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Abstract
Allogeneic major histocompatibility complex class I molecules induce strong cytotoxic T lymphocyte (CTL) responses whereas xenogeneic molecules do not. We have tested a series of mouse/human hybrid molecules for their ability to stimulate mouse CTL. The molecules with murine α3 domains consistently stimulated stronger CTL responses than those with human α3 domains, independent of the species origin of the N‐terminal α1 or α2 domains. We have found that the ability of class I molecules to induce strong cytotoxic responses correlates positively with their ability to stimulate expansion of the CD8+CD4− T cell subset. The results indicate that mouse T cells can recognize class I molecules with human α1 and/or α2 domains, but for efficient stimulation of these T cells it is important that the immunizing molecule contains a murine α3 domain. We suggest that T cell priming requires an efficient interaction of CD8 with the class I α3 domain, and this shows some species restriction.