Molecular basis of immune recognition
201 MOLECULAR BASIS OF IMMUNE RECOGNITION JACK L. STROMINGER, Harvard University, Department of B iochemistry and Molecular Biology, 7 Div in i ty Avenue, Cambridge, MA, 02138, U.S.A. The molecules now known to be involved in immune recognit ion wi l l be reviewed. These include, ih addit ion to the foreign antigens, a class I or class II MHC molecule (the restr ict ing element), the T cell receptor (of which two types are now known, TCRa~ and TCR'~E) and various molecules thought to be involved in "stabi l iz ing" interact ions (including LFA and VLA proteins, CD2, CD4 and CD8). Many autoimmune diseases, including mult ip le sclerosis, have been l inked to part icu lar al leles of class II MHC products. Of the 15 genes or gene fraoments in the class II region of the human 5~C, only 4 ~ chain genes and 3 e chain genes are known to be expressed as protein leading to 4 pr inc ip le subsets of class II antigens (DR, DR(MT), DQ and DP) . The possible express ion of addi- t ional proteins wi l l be discussed. In the l imited examples in man in which the al lele to which the disease is l inked has been sequenced from a patient, that al lele is identical to the one found in normal controls. Thus the "disease al lele" need not be abnormal. However, in one exper imental model (the non- obese d iabet ic mouse) an abnormal al lele has been found in associat ion with the disease. The possible role of T cell receptors in auto immunity needs care- ful attention. Data relat ing to the recently d iscovered TCRyA, which can part ic ipate in a non-MHC restr icted kil l ing, wi l l be presented. PARANEOPLASTIC AUTOIMMUNITY ANDREAS J. STECK, Department of Neurology, CHUV, I011 Lausanne, Switzerland In the last few years, a large amount of data has accumulated, showing that a high proportion of monoclonal (M) Ig, usual ly belonging to the IgM class in patients with peripheral neuropathy, have antibody act iv i ty against various nervous tissue antigens ( I ) . Biochemical and immunological analyses have shown that the usual target antigens in these patients are carbohydrate structures of glycoproteins and g lyco l ip ids . Numerous studies have demonstrated that one of the most frequently reported autoantibody act iv i t ies of human M-IgM is di - rected towards the MAG/HNK-I epitope which is a carbohydrate determinant shared by several glycoproteins and g lyco l ip ids . But other autoantibody act iv i t ies against gangliosides or phosphorylated epitopes should prove to be re la t ive ly frequent among M-IgM. From a c l in i ca l point of view there appears to be a cer- tain spec i f i c i ty between the chief type of nerve in jury and antibody act iv i ty . Patients with anti-MAG antibodies have a demyelinating sensory-motor neuro- pathy while patients with antibodies to gangliosides GMI and GD]b have a motor neuron disease l ike syndrome. The rea l i zat ion that these diverse carbohydrate structures are found in important cel l surface macromolecules may point to a role for these glycoconjugates as receptors for regulators of ce l l - ce l l in ter - actions and d i f fe rent ia t ion . The analysis of new antibody spec i f i c i t ies and study of the i r c ross - react iv i ty may help us to understand better the neuro- logic manifestations of paraneoplastic syndromes that af fect the nervous system. I. Peripheral neuropathy associated with monoclonal IgM autoantibody. Steck A. J . , Murray N., Dellagi K., Brouet J .C., Seligmann M. Annals Neurol. ( in press).