ANALYSIS OF THE REQUIREMENT FOR BETA-2-MICROGLOBULIN FOR EXPRESSION AND FORMATION OF HUMAN CD1 ANTIGENS

Human CD1 form a group of nonpolymorphic leukocyte surface molecules w ith homology to major histocompatibility complex (MHC) proteins. Recen t findings in human and in mouse demonstrate the capacity of CD1 molec ules to present nonpeptide components like lipids or lipoglycans as we ll as peptides. We studied the involvement of beta 2-microglobulin (be ta 2m) in expression of the classic human CD1 proteins CD1a, CD1b, and CD1c. The beta 2m-deficient human melanoma cell line FO-1 was transie ntly transfected with either CD1a, CD1b, or CD1c DNA alone, or in comb ination with beta 2m using the adenovirus-enhanced receptor-mediated t ransfer infection system. Only co-transfection of FO-1 cells with CD1 + beta 2m resulted in the detection of CD1 Ag by monoclonal antibodies (mAb). This indicated that CD1 mAb recognized determinants are depend ent on beta 2m and raised the question whether beta 2m-free forms of C D1 can be expressed. Therefore, to visualize CD1 molecule expression i ndependently of beta 2m, we expressed tagged recombinant forms. A full -length CD1b construct tagged at the very C terminus with a small pept ide was transported to the plasma membrane only when beta 2m was co-tr ansfected. beta 2m involvement in the transport of CD1 was confirmed b y expression of soluble forms of CD1a, CD1b, and CD1c in three differe nt cell types. Analogous to tagged full-length CD1b, secretion of the soluble CD1 constructs was strictly dependent on beta 2m. The soluble CD1 chimeras were secreted as complexes with endogenous beta 2m. Thus, similar to its role for MHC class I expression, beta 2m is essential for processing and surface transport of the classic human CD1 molecule s CD1a, CD1b, and CD1c.