34 - Brain microvessel antigens

Summary

Introduction

Understanding the structure–function relationship of the BBB depends on the identification of the molecular components involved. One approach to address this topic is based on the generation of monospecific antibodies starting typically from heterogeneous immunogen fractions. The resulting antibodies are then used to identify the corresponding antigens and determine their function, therefore following a structure-to-function strategy. This chapter is focused on antigens of this experimental history, whereas antibodies for characterized vascular endothelial proteins such as glucose transporters, transferrin-and VEGF receptors, junction proteins etc. will be discussed elsewhere. Besides being helpful to reveal the molecular architecture of the BBB, antigens could be employed as diagnostic indexes to evaluate BBB integrity under pathological conditions in vivo or, for example, as differentiation markers in in vitro models.

HT7/Neurothelin

One of the most thoroughly studied antigens present on brain micro vessels is HT7/neurothelin. In two independent approaches using as immunogens either tissue homogenates or purified cell membranes of the embryonic chicken retina, monoclonal antibodies (MAb) HT7 and 1W5 were generated. The corresponding antigens, which have subsequently been shown to be identical, have been termed HT7 (Risau et al., 1986) and neurothelin (Schlosshauer and Herzog, 1990), respectively. As deduced from cDNA sequencing, the antigen has 246 amino acids with a predicted molecular weight of 26 893 daltons.