CONTROL OF MHC CLASS-II GENE-EXPRESSION IN AUTOIMMUNE, INFECTIOUS, AND NEOPLASTIC DISEASES

The major histocompatibility complex (MHC) class II genes encode surfa ce molecules that are required for presentation of antigenic peptides to helper T-cells. The concentration of these proteins on the surface of effector cells (antigen-presenting cells such as B-cells and macrop hages) is one of the parameters affecting the intensity of the immune response. Many studies have thus focused their attention on the mechan isms that control the expression of class II genes, particularly in B- cells. The anatomy of MHC class II promoters has been dissected in det ail, and many trans-acting factors and their cognate DNA regulatory el ements have been identified and characterized, thus helping to elucida te the molecular circuitry which determines tissue-specific, coordinat e expression of these genes. In most cases, regulation has been invest igated at the level of mRNA transcription. MHC class II gene expressio n has been observed as well, under physiological conditions, in many o ther tissues and organs such as brain, thyroid, thymus, and intestine, thus implying that class II molecules may be involved, whether direct ly or indirectly, in the modulation of other important biological resp onses in addition to the control of the immune reaction against solubl e antigens. Spurious MHC class II activity is also detected in tumor c ells and in other pathological conditions such as those found in autoi mmune, inflammatory, and infectious diseases. In autoimmunity, cells t hat express class II molecules may present tissue-specific antigens, t hus triggering a mechanism of self-destruction. In tumors, instead, un scheduled MHC class II expression may be part of a mechanism that prev ents tumor progression. Comprehension of the regulatory functions oper ating in pathological conditions as compared to those active in B-cell s and in macrophages is still rudimentary. Because of the possible pat hogenetic importance of aberrant class II expression, knowledge of the cis- and trans-acting elements controlling gene expression at either the transcriptional or posttranscriptional level may allow the develop ment of strategies for immunointervention against these diseases.