Cytotoxic T lymphocytes (CTL) have been implicated as effectors in allograft rejection and in control of viral infection. Induction of a cytolytic response requires T cell recognition of foreign major histocompatibility complex (MHC) class I glycoproteins, or syngeneic MHC antigens along with a foreign (i.e., viral) protein. This recognition process leads to proliferation and differentiation of precursor cells to effector CTL capable of lysing target cells that bear the same antigens. While class I oligosaccharide residues do not contribute to serologic determinants (1-4) their role in T cell recognition has remained unclear. Modification of the carbohydrates of membrane glycoproteins on intact stimulating or target cells has been observed to inhibit (1, 5, 6), stimulate (7, 8), or have no effect (2, 6, 9) on T cell responses. In all of these cases, it is difficult to conclude whether the observed effects were due to altered MHC antigen oligosaccharides, since modifications could not be limited to the surface glycoprotein of interest, and the extent of modification could not be readily determined.Class I antigens of the murine MHC (H-2) are polymorphic two-chain cell surface glycoproteins consisting of a glycosylated transmembrane heavy chain (Mr 40,000-50,000) noncovalently associated with /32-microglobulin, an invariant, nonglycosylated polypeptide (Mr 1 1,500). Amino acid and DNA sequence data suggest that the extracellular portion of the heavy chain can be divided into three globular domains of ~91 amino acids each (~, c~z, and as). Determinants recognized by T cells appear to reside in the c~l and a2 domains (10), regions of maximal amino acid variability (11). Glycosyl moieties are also present in these regions, N-linked to asparagine residues at positions 86 and 176. A third glycan attachment site in K d, D b, and L d antigens is at residue 256 (11).Purified class I alloantigen in artificial membranes (liposomes) can stimulate a CTL response of comparable magnitude to that obtained using intact stimulating cells when added to in vitro cultures of spleen cells from mice previously primed to the same alloantigen (12). The magnitude of the response to the liposomes provides a direct measure of the effectiveness of antigen recognition