MONOCLONAL-ANTIBODY TO TYPE-IV COLLAGEN WITH SELECTIVE BASEMENT-MEMBRANE LOCALIZATION

Abstract

A monoclonal antibody (MCA IV-1) was developed to be determinant of the high MW fractions of human placental collagen, present also in bovine lens capsule and glomerular basement membrane type IV collagens. This unique determinant is pepsin and collagenase resistant and is apparently distinct from the .alpha.1 (IV) and .alpha.2 (IV) helical peptides. As part of the high MW molecules, the determinant is located in a region additively deformable by reduction and sodium dodecyl sulfate denaturation. When a 20-kilodalton, largely collageneous, fragment containing this determinant is separated from the larger fraction by 37.degree. C collagenase treatment, the determinant is insensitive to reduction or sodium dodecyl sulfate denaturation. Immunohistologic analysis and comparison with a polyclonal antibody to type IV collagen shows a marked selectivity of localization in the glomerular basement membrane. MCA IV-1 reacts in the inner aspect of the glomerular basement membrane but primarily in the mesangium, where it selectively expands in diabetic nephropathy. Tissue selectivity is also evident in lens and corneal basement membrane.