The major histocompatibility complex (MHC) is a chromosomal region that has been extensively characterized in several mammals, particularly man and mouse (Flavell et al., 1986 and Ploegh et al., 1981). The region which represents about 0.1% of the total genome in mouse, comprises a large number of genes classified into class I and class II MHC genes encoding a large number of polymorphic class I or class II MHC molecules respectively. Class I genes include HLA-A, B, C genes in man and H-2D, K, L in the mouse. Class II MHC genes include HLADR, DP, DQ in human and H-2IA and IE genes in the mouse. Class I MHC molecules are made of a highly polymorphic glycosylated transmembrane α-chain of about 45 kDa, associated with a non-polymorphic, nonglycosylated, 12-kDa chain, called β2-microglobulin, not encoded within the MHC locus. Class II molecules encoded entirely within the MHC locus are made of two transmembrane polymorphic chains, α and β, which associate to form heterodimer. Class I heavy and light chains comprise three and one extracellular domains respectively, whereas both α and β chains of class II molecules have two extracellular domains each. Both class I and class II MHC antigens show very high polymorphism and two of the extracellular domains, α1 and α2 in class I and α1 and β1 in class II heterodimers display much more variability within different alleles than the other so called constant domains (α3 and β2 in class I and α2 and β2 in class II molecules). Constant domains resemble immunoglobulin domain, which make MHC molecules members of the immunoglobulin super family (Williams et al., 1988). Class I molecules are constitutively expressed on most types of nucleated cells. Class II molecules are expressed largely by cells of immune lineage, particularly B cells, macrophages, and dendritic cells. MHC class I molecules present antigenic peptides to CD8+ T cells. The majority of class I-binding peptides are derived from nuclear and cytosolic proteins. MHC class II molecules present peptides from antigens degraded by the endosomal/lysosomal pathway to CD4+ T cells (Benham et al., 1995). Antigen receptor on T-cells (T-cell receptor or TCR) can recognize antigenic peptides only when the latter are presented associated with class I or class II MHC antigens. In addition, during T-cell differentiation, only those T-cells are permitted to develop which can recognize antigen associated with self MHC molecules, a phenomenon which is referred to as MHC restriction (Zinkernagel et al., 1979). While T-cells can only be activated in a MHC restricted manner, a class of non-T cytotoxic lymphocytes called natural killer (NK) cells, can spontaneously kill target cells in a MHC non-restricted manner. Levels of expression of class I MHC antigens on tumor cells however determine the susceptibility of tumor cells to NK cells (Haridas and Saxena, 1995a, 1995b, Saxena et al., 1996). Expression of class I MHC molecules thus play a crucial role in determining the susceptibility of target cells to both T cells and NK cells.