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The lymphocyte function-associated 1 (LFA-1), ~ Mac-l, and p150,95 molecules constitute a family of structurally and functionally related, high molecular weight, human leukocyte surface glycoproteins (1). Each molecule contains an a and a 3 subunit noncovalently associated in an al31 structure. The 3 subunits of Mr 95,000 in each of these three molecules are identical. The molecules are distinguished by their a subunits, which have different isoelectric points, molecular weights, and cell distributions, and are immunologically non-cross-reactive. The relative molecular weights of the Mac-l, LFA-1, and p150,95 a subunits are 165,000, 177,000, and 150,000 for aM, aL, and aX, respectively. This glycoprotein family is conserved in mouse and human (1, 2). In both species, the a and 3 subunits of each molecule are biosynthesized as separate a ' and ~' intracellular precursors (1, 3). The precursors associate into a ' ~ ' complexes, are processed to the mature a3 form, and then transported to the cell surface. The murine aM and aL subunits have 33% amino acid sequence homology with one another. 2 Such homology suggests that a primordial a chain gene duplication event(s) led to the evolution of this glycoprotein family. The LFA-1 and Mac-1 molecules contribute to multiple types of leukocyte adhesion reactions. The LFA-1 molecule participates in the formation of adhesions between effector and target cells in cytolytic T lymphocyte-mediated killing and in natural killing, as shown by monoclonal antibody (mAb) blocking experiments (4-6). LFA-1 also participates in T helper cell responses, and its distribution on B cells, granulocytes, and monocytes suggests it may function in adhesion of these cells as well (7). Mac-1 has been defined (8) by mAb as a mouse differentiation antigen present on myeloid and absent on lymphoid cells. SubseThis work was supported by grants CA 31798, CA 31799, and AI 19031 from the National Institutes of Health, an American Cancer Society Faculty Award to T. Springer, and an NIH Research Career Development award to D. Anderson. 1 Abbreviations used in this paper: CR1, 3, complement receptor types 1 and 3; EBV, Epstein-Barr virus; FCS, fetal calf serum; FITC, fluorescein isothiocyanate; IL-2, interleukin 2; LFA-1, lymphocyte function-associated antigen 1; mAb, monoclonal antibody; PAGE, polyacrylamide gel electrophoresis; PBS, phosphate-buffered saline; PHA, phytohemagglutinin; SDS, sodium dodecyl sulfate. Springer, T. A., D. Teplow, and W. J. Dreyer. The LFA-1, Mac-1 family of leukocyte adhesion glycoproteins: alpha subunit sequence homology and unexpected relation to leukocyte interferon. Manuscript submitted for publication.