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MOLECULAR BASIS OF IMMUNE RECOGNITION

JACK L. STROMINGER, Harvard University, Department of Biochemistry and Molecular

Biology, 7 Divinity Avenue, Cambridge, MA, 02138, U.S.A.

The molecules now known to be involved in immune recognition will be reviewed.

These include, ih addition to the foreign antigens, a class I or class II MHC

molecule (the restricting element), the T cell receptor (of which two types are

now known, TCRa~ and TCR'~E) and various molecules thought to be involved in

"stabilizing" interactions (including LFA and VLA proteins, CD2, CD4 and CD8).

Many autoimmune diseases, including multiple sclerosis, have been linked to

particular alleles 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 principle subsets of

class II antigens (DR, DR(MT), DQ and DP) . The possible expression of addi-

tional proteins will be discussed. In the limited examples in man in which the

allele to which the disease is linked has been sequenced from a patient, that

allele is identical to the one found in normal controls. Thus the "disease

allele" need not be abnormal. However, in one experimental model (the non-

obese diabetic mouse) an abnormal allele has been found in association with

the disease. The possible role of T cell receptors in autoimmunity needs care-

ful attention. Data relating to the recently discovered TCRyA, which can

participate in a non-MHC restricted killing, will be presented.

PARANEOPLASTIC AUTOIMMUNITY

ANDREAS J. STECK, Department of Neurology, CHUV, I011 Lausanne, Switzerland

In the las t few years, a large amount of data has accumulated, showing that a high proport ion of monoclonal (M) Ig, usual ly belonging to the IgM class in pat ients with peripheral neuropathy, have antibody a c t i v i t y against various nervous t issue antigens ( I ) . Biochemical and immunological analyses have shown that the usual target antigens in these pat ients are carbohydrate structures of glycoproteins and g l yco l i p i ds . Numerous studies have demonstrated that one of the most f requent ly reported autoantibody a c t i v i t i e s of human M-IgM is d i - rected towards the MAG/HNK-I epitope which is a carbohydrate determinant shared by several g lycoproteins and g l yco l i p ids . But other autoantibody a c t i v i t i e s against gangliosides or phosphorylated epitopes should prove to be r e l a t i v e l y frequent among M-IgM. From a c l i n i c a l point of view there appears to be a cer- ta in s p e c i f i c i t y between the ch ie f type of nerve in ju ry and antibody a c t i v i t y . Patients with anti-MAG antibodies have a demyelinating sensory-motor neuro- pathy whi le pat ients wi th ant ibodies to gangliosides GMI and GD]b have a motor neuron disease l i ke syndrome. The rea l i za t i on that these diverse carbohydrate structures are found in important ce l l surface macromolecules may point to a role for these glycoconjugates as receptors fo r regulators of c e l l - c e l l i n te r - actions and d i f f e r e n t i a t i o n . The analysis of new antibody s p e c i f i c i t i e s and study of t he i r c r oss - reac t i v i t y may help us to understand better the neuro- logic manifestat ions of paraneoplastic syndromes that a f fec t the nervous system.

I . Peripheral neuropathy associated with monoclonal IgM autoantibody. Steck A.J . , Murray N., Del lagi K., Brouet J.C., Seligmann M. Annals Neurol. ( in press).