The Conformational Flexibility and β ₂-Microglobulin Interaction Dynamics of the H-2K^b Heavy Chain

Abstract

The expressed gene products of the class I major histocompatibility complex (MHC) are now recognized as key elements in the mechanism used by cytotoxic T-lymphocytes (CTLs) to detect virus-infected cells (Doherty and Bennick 1981). Although it is widely accepted that CTL antigen receptors can only recognize viral antigens when they are “seen” in association with self class I molecules (i.e., the phenomenon of MHC-restricted recognition; Zinkernagel and Doherty 1979), it has not yet been established how, in molecular terms, the class I molecules “present” viral determinants to CTL receptors. In fact, it is not even clear where the self and nonself components of the target structure intersect within an infected cell. Particularly useful in this regard would be a better understanding of the class I heavy chain dynamics within the cell: the nature of its association with β ₂-microglobulin (β ₂m) postbiosynthesis, the possibility for subsequent dissociation and reassociation with β ₂m or other molecules, as well as the conformational perturbation accompanying the different subunit interactions. Defining the spectrum of interaction sites and conformational states available to class I heavy chains should contribute to establishing which of these are most important with respect to its antigen presentation function.