Sequence homology of the LFA-1 and Mac-1 leukocyte adhesion glycoproteins and unexpected relation to leukocyte interferon

Abstract

Cell-surface adherence reactions are fundamental to the biology of lymphocytes, monocytes and granulocytes. The lymphocyte function-associated 1 (LFA-1) and macrophage 1 (Mac-1) glycoproteins mediate differing types of adhesion reactions on these cells. LFA-1 participates in T-lymphocyte and natural killer-cell adhesion to target cells^1–3, whereas the Mac-1 antigen is identical to the complement receptor type 3, which mediates adhesion of monocytes and granulocytes to C3bi-sensitized particles⁴. Deficiency of these proteins, in a heritable disease, results in multiple adhesion-related leukocyte defects^5,6. LFA-1 and Mac-1 resemble one another in overall structure, having α-subunits of relative molecular mass (M_r) 180,000 and 170,000, respectively, which are non-covalently associated with β-subunits of M_r 95,000 in α₁β₁, complexes^7,8. Peptide mapping and immunological cross-reactivity have shown that the β-subunits are highly related if not identical, but have revealed no similarities between the α-subunits^7,9,10. Nonetheless, the shared β-subunit suggested that LFA-1 and Mac-1 might be members of a protein family containing diversified but evolutionarily related α-subunits. Therefore, we examine here the structure of the α-subunits by N-terminal amino-acid sequencing. Sequence homology shows that the α-subunits are members of a novel leukocyte adhesion protein family, and suggests that their evolution occurred by gene duplication. A search for similarities to previously sequenced proteins reveals a further unexpected homology between LFA-1 and leukocyte (α) interferons.