EXPRESSION OF A NOVEL INTEGRIN BETA-1 CHAIN EPITOPE AND ANTI-BETA(1) ANTIBODY-MEDIATED ENHANCEMENT OF FIBRONECTIN-BINDING ARE DEPENDENT ON THE STAGE OF T-CELL DIFFERENTIATION

beta(1) integrins are a family of alpha beta heterodimers that serve as cell surface receptors for extracellular matrix proteins. We demonstrate that the anti-mouse integrin beta(1) chain mAb KMI6 selectively recognizes a beta(1) epitope that is constitutively expressed by certain immature thymocytes and is induced only slightly on mature thymocytes and peripheral T cells by activation with Con A. Because virtually all cells examined expressed beta(1) integrins on their surface, expression of the KMI6 epitope is T cell differentiation stage specific. Most CD3(-)4(-)8(-) thymocytes were KMI6(+), with the lowest level of staining observed on the earliest CD44(+)IL-2R(-) cells within this subset. Expression was down-regulated during the CD3(-)4(-)8(-) to CD3(-)4(-)8(+) transition, and lost by the CD4(+)8(+) stage. Mature single positive thymocytes and resting peripheral T cells were also KMI6(-). In contrast with the loss of the epitope before TCR expression by other thymocytes, most CD3(+)4(-)8(-) and certain CD8(+) gamma delta TCR(+) thymocytes were KMI6(+) Addition of KMI6 to cell adhesion assays enhanced CD4(-)8(-) thymocyte, but not activated mature thymocyte or peripheral T cell, binding to fibronectin (via alpha(4) beta(1) and alpha(5) beta(1)), whereas laminin binding (via alpha(6) beta(1)) was unaffected. These properties distinguish the KMI6 epitope from other epitopes involved in beta(1) integrin activation in mice and other species. The unique selectivity of KMI6 recognition of beta(1) integrins, and its selective enhancement of ligand binding suggest that beta(1) integrin structure and factors that regulate beta(1) integrin binding are correlated with the stage of T cell differentiation.