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Human CTL clones specific for myelin basic protein are HLA class II restricted
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l o c a l i s i n g the p o s i t i o n of the g l y c o s y l a t i o n site ( a s p a r a g i n e 141) in r e l a t i o n to the m . a b r e g i o n s ; (2) d e f i n i n g the a m i n o a c i d s e q u e n c e s i n v o l v e d in m . a b b i n d i n g by (a) c o m p e t i t i o n w i t h a n t i b o d i e s a g a i n s t s y n t h e t i c p e p t i d e s a n d (b) b i n d i n g to l a r g e r p e p t i d e s e q u e n c e s of h u m a n A C h R c l o n e d a n d e x p r e s s e d in E . c o l i .
HUMAN
CTL
W.
CLONES SPECIFIC FOR MYELIN BASIC PROTEIN H L A C L A S S II R E S T R I C T E D
Weber,
ARE
W.
Buurman, Z. Jingwu, a n d J. R a u s University Llmburg, BELGIUM, and Surgery, Academic Hospital M a a s t r l c h t , THE NETHERLANDS
Dr.L.Wlllemslnstltute, Depts.of
Neurology
Multiple Sclerosis (MS) is a neurological disease in w h i c h cellullar i m m u n e reactions against the auto-antlgen M y e l i n Basic Protein are hypothesized to m e d i a t e nervous tissue destruction. W e h a v e isolated f r o m t h e p e r i p h e r a l blood of t h r e e M S patients, CD@+ T cell clones specific for MBP. T h e s e clones proliferate specifically in response to MBP, are capable of producing InterleuKin a and Interferon-T. More importantly, these clones were capable of MBP-speclflc lysls, as measured by a newly developed assay, l n v o l v l n g 51Cr-labelled autologous Epstein-Barr virus transformed B cells, c o a t e d w l t h MBP. T h e H L A restriction pattern of specific p r o l i f e r a t i v e a n d cytolytlc f u n c t i o n of t h e MBP-specific T lymphocyte clones w a s analysed uslnK monoclonal antibodies against various HLA gene products, and using allogenelc EBV-transformed B cells as antlgen-presenting cells a n d as t a r g e t s for cytolysls. It a p p e a r e d t h a t specific f u n c t i o n of t h e T cell clones w a s r e s t r i c t e d b y H L A class II antigens, a n d m o r e specifically, b y molecules d e f i n e d b y D R locus genes. It t h u s a p p e a r e d t h a t t h e a u t o - l m m u n e T cell clones we h a v e generated f r o m M S p a t i e n t s express a functional r e p e r t o l r similar to t h e MBP-speclflc T cell lines m e d i a t i n g experimental autoimmune e n c e p h a l o m y e l i t i s in t h e rat. T h e s e h u m a n auto-lmmune T lymphocyte clones provlde important tools to study the pathogenesis of MS.
ANTIBODY CROSS-REACTIVITY BETWEEN MYELIN BASIC PROTEIN AND ANTIGEN OF T CELLS : IMPLICATIONS FOR AUTO-IMMUNITY. W. Dr.
Weber,
Z. J i n g w u ,
J. Borst,
W.
Buurman,
J.
CD3
Raus
L. W l l l e m s l n s t l t u u t , DlepenbeeK, BELGIUM, Academic Hospital Maastricht, Maastrlcht, The Netherlands Cancer Institute, Amsterdam, THE NETHERLANDS.
This report describes cross-reactlvlty between two blologically important human cell surface molecules, namely Myelin Basic Protein (MBP) and CD3 antigen of T cells, as recognized by a murlne monoclonal antibody (MAb) WW.BI. MBP, a protein essential to signal c o n d u c t i o n In t h e central nervous
l o c a l i s i n g the p o s i t i o n of the g l y c o s y l a t i o n site ( a s p a r a g i n e 141) in r e l a t i o n to the m . a b r e g i o n s ; (2) d e f i n i n g the a m i n o a c i d s e q u e n c e s i n v o l v e d in m . a b b i n d i n g by (a) c o m p e t i t i o n w i t h a n t i b o d i e s a g a i n s t s y n t h e t i c p e p t i d e s a n d (b) b i n d i n g to l a r g e r p e p t i d e s e q u e n c e s of h u m a n A C h R c l o n e d a n d e x p r e s s e d in E . c o l i .
HUMAN
CTL
W.
CLONES SPECIFIC FOR MYELIN BASIC PROTEIN H L A C L A S S II R E S T R I C T E D
Weber,
ARE
W.
Buurman, Z. Jingwu, a n d J. R a u s University Llmburg, BELGIUM, and Surgery, Academic Hospital M a a s t r l c h t , THE NETHERLANDS
Dr.L.Wlllemslnstltute, Depts.of
Neurology
Multiple Sclerosis (MS) is a neurological disease in w h i c h cellullar i m m u n e reactions against the auto-antlgen M y e l i n Basic Protein are hypothesized to m e d i a t e nervous tissue destruction. W e h a v e isolated f r o m t h e p e r i p h e r a l blood of t h r e e M S patients, CD@+ T cell clones specific for MBP. T h e s e clones proliferate specifically in response to MBP, are capable of producing InterleuKin a and Interferon-T. More importantly, these clones were capable of MBP-speclflc lysls, as measured by a newly developed assay, l n v o l v l n g 51Cr-labelled autologous Epstein-Barr virus transformed B cells, c o a t e d w l t h MBP. T h e H L A restriction pattern of specific p r o l i f e r a t i v e a n d cytolytlc f u n c t i o n of t h e MBP-specific T lymphocyte clones w a s analysed uslnK monoclonal antibodies against various HLA gene products, and using allogenelc EBV-transformed B cells as antlgen-presenting cells a n d as t a r g e t s for cytolysls. It a p p e a r e d t h a t specific f u n c t i o n of t h e T cell clones w a s r e s t r i c t e d b y H L A class II antigens, a n d m o r e specifically, b y molecules d e f i n e d b y D R locus genes. It t h u s a p p e a r e d t h a t t h e a u t o - l m m u n e T cell clones we h a v e generated f r o m M S p a t i e n t s express a functional r e p e r t o l r similar to t h e MBP-speclflc T cell lines m e d i a t i n g experimental autoimmune e n c e p h a l o m y e l i t i s in t h e rat. T h e s e h u m a n auto-lmmune T lymphocyte clones provlde important tools to study the pathogenesis of MS.
ANTIBODY CROSS-REACTIVITY BETWEEN MYELIN BASIC PROTEIN AND ANTIGEN OF T CELLS : IMPLICATIONS FOR AUTO-IMMUNITY. W. Dr.
Weber,
Z. J i n g w u ,
J. Borst,
W.
Buurman,
J.
CD3
Raus
L. W l l l e m s l n s t l t u u t , DlepenbeeK, BELGIUM, Academic Hospital Maastricht, Maastrlcht, The Netherlands Cancer Institute, Amsterdam, THE NETHERLANDS.
This report describes cross-reactlvlty between two blologically important human cell surface molecules, namely Myelin Basic Protein (MBP) and CD3 antigen of T cells, as recognized by a murlne monoclonal antibody (MAb) WW.BI. MBP, a protein essential to signal c o n d u c t i o n In t h e central nervous