1398 Definition of Multiple T Cell Epitopes On

T h e i m m u n e system of an organism is requi red to be capab le of responding to a wide spec t rum of antigens. T helper cells recognize these ant igens in associat ion with Ia molecules. Given that the number of different Ia molecules encoded in the genome is l imited, the possible restr ict ion specificities of the T cells would appea r to be s imilar ly l imited. However , if T cells could use more than one restr ict ion site per molecule, the immune response capab i l i ty of the organism would be enlarged. T h r o u g h the use of monoclonal an t ibodies and monoclona l T cell lines, it has been possible to establish tha t an ind iv idua l cloned T cell line, be it a l loreact ive or ant igenreactive, has specificity for one Ia molecule (1). Al though it has not yet been possible to isolate and character ize the T cell receptor for ant igen, studies on cloned T cell lines can provide indirect in format ion about the receptor by ana lyz ing the na tu re and variety of de te rminan t s with which the receptor interacts. These studies might also reveal in format ion about the n u m b e r of funct ional ly impor t an t epi topes on the Ia molecules. Recent ly , there have been reports descr ibing the defini t ion of several serological epi topes on I-A k molecules (2, 3). I f T cells also can recognize more than one epi tope on an Ia molecule, then one would expect to be able to find ind iv idua l T cell clones specific for each epitope. A m o n g the I-Ab-restr icted a l loreact ive clones in our collection, we have ident if ied one that is capab le of recognizing cells of the s train B6.C-H-2 bin12, the I -A b mutan t , whereas the o ther I-A b restr ic ted clones cannot . Addi t iona l ly , we have found tha t two clones that are specific for the AbA~ hybr id molecule also can recognize b m l 2 cells, a l though they do not respond at all to the paren t s train B6 cells. One of these two clones is an al loreact ive A anti-(B6 X A)F1 clone, whereas the o ther is a L-glutamic acid6°-r-alanine~°-L-tyrosine 1° (GAT)-react ive clone of (B6 x A)F1 origin. The ident i f icat ion of these two dist inct react iv i ty pa t te rns suggests that there exist both on IA b molecules and on hybr id b k A~A B molecules at least two dist inct epi topes recognized by T cells. Add i t iona l da t a ob ta ined by s tudying monoclona l an t i I -A a n t i b o d y inhib i t ion of s t imula t ion of T cell clones demons t ra te a lack of ident i ty between serologically defined epi topes on I-A molecules and epi topes on I-A molecules recognized by cloned T cell lines.