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Abstract Details

Characterization of Myelin-reactive CD8+ T cells in Multiple Sclerosis
Multiple Sclerosis
P2 - Poster Session 2 (5:30 PM-6:30 PM)
15-065
To determine if there are quantitative and/or qualitative differences in myelin-specific CD8+ T cell populations in the peripheral blood of MS patients and control subjects. 
CD8+ T cells are thought to play an important role in the pathogenesis of multiple sclerosis (MS), yet their antigen specificity and function remains poorly defined.  Myelin antigens are considered putative auto-antigens implicated in MS.  Although certain myelin-reactive CD8+ T cell populations have been previously described, efforts to accurately quantify and phenotype them have been hampered by their low frequencies. 
We constructed a panel of myelin peptide MHC I (pMHC I) tetramers to screen for candidate myelin-specific CD8+ T cell populations from the peripheral blood of MS patients.  Tetramer-positive CD8+ T cells were enriched by cell sorting followed by in vitro expansion to validate pMHC I tetramer specificity.  Myelin-specificity was then confirmed by demonstrating functional reactivity to cognate myelin antigen.  Using a combinatorial tetramer staining paradigm, we quantified the precursor frequencies of validated myelin CD8+ T cell epitopes in untreated RR-MS patients and HLA-matched healthy controls.  We also performed phenotyping analysis of myelin tetramer-positive CD8+ T cells using a panel of cell surface markers.

We have identified several previously established as well as novel human myelin CD8+ T cell epitopes using tetramers.  Myelin-specific CD8+ T cells are present at variable, but detectable frequencies in the peripheral blood of MS patients and control subjects.  Certain populations of myelin-specific CD8+ T cells also show evidence of antigen experience in MS patients. 

In our detailed ex vivo analysis of myelin-specific CD8+ T cells, we have detected reactivity to novel and previously identified epitopes in the blood of MS patients and control subjects.   The finding that myelin-specific CD8+ T cells show evidence of prior antigen exposure in MS patients suggests they may play a role in the disease process. 
Authors/Disclosures
Joseph J. Sabatino, Jr., MD (University of California San Francisco)
PRESENTER 		The institution of Dr. Sabatino has received research support from Roche/Genentech.
Michael R. Wilson, MD, FAAN (University of California San Francisco) Dr. Wilson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Pfizer. Dr. Wilson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Ouro Medicines. Dr. Wilson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Vertex Pharmaceuticals. Dr. Wilson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Indapta Therapeutics. Dr. Wilson has received personal compensation in the range of $50,000-$99,999 for serving as an officer or member of the Board of Directors for Delve Bio. Dr. Wilson has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Cambridge Medical Experts. Dr. Wilson has received personal compensation in the range of $5,000-$9,999 for serving as an Expert Witness for Dunham Hallmark. Dr. Wilson has stock in Delve Bio. The institution of Dr. Wilson has received research support from Genentech / Roche. The institution of Dr. Wilson has received research support from NIH. The institution of Dr. Wilson has received research support from Novartis. The institution of Dr. Wilson has received research support from National Multiple Sclerosis Society. The institution of Dr. Wilson has received research support from Fanconi Anemia Research Foundation. The institution of Dr. Wilson has received research support from Department of Defense. The institution of Dr. Wilson has received research support from Chan Zuckerberg Initiative. The institution of Dr. Wilson has received research support from Kyverna Therapeutics. Dr. Wilson has received intellectual property interests from a discovery or technology relating to health care. Dr. Wilson has received intellectual property interests from a discovery or technology relating to health care. Dr. Wilson has received personal compensation in the range of $10,000-$49,999 for serving as a Expert Witness with US Dept of Justice.
Peter A. Calabresi, MD, FAAN (Johns Hopkins University) Dr. Calabresi has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Novartis. Dr. Calabresi has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Lilly. Dr. Calabresi has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Idorsia. An immediate family member of Dr. Calabresi has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for MyMD. Dr. Calabresi has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Myelin Repair Foundation. The institution of Dr. Calabresi has received research support from Genentech. Dr. Calabresi has received publishing royalties from a publication relating to health care. Dr. Calabresi has received personal compensation in the range of $500-$4,999 for serving as a Study Section Member with NIH. Dr. Calabresi has received personal compensation in the range of $500-$4,999 for serving as a Grant reveiwer with Myelin Repair Foundation. Dr. Calabresi has received personal compensation in the range of $500-$4,999 for serving as a Speaker for CME with NYAS. Dr. Calabresi has received personal compensation in the range of $500-$4,999 for serving as a Speaker with Academic CME.
Stephen L. Hauser, MD (UCSF Weill Institute for Neurosciences) Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for NGM Bio. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Moderna. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BD. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Pheno Therapeutics. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Nurix Therapeutics. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Gilead. Dr. Hauser has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Accure. Dr. Hauser has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alector. Dr. Hauser has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Hinge Therapeutics. Dr. Hauser has received personal compensation in the range of $10,000-$49,999 for serving as an officer or member of the Board of Directors for Neurona. Dr. Hauser has a non-compensated relationship as a Clinical Trial/Primary Investigator with Roche that is relevant to AAN interests or activities. Dr. Hauser has a non-compensated relationship as a Clinical Trial/Primary Investigator with Novartis that is relevant to AAN interests or activities.
No disclosure on file
Scott S. Zamvil, MD, PhD, FAAN (University of CA, San Francisco) Dr. Zamvil has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Sanofi-Genzyme. Dr. Zamvil has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Alexion. Dr. Zamvil has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Genzyme. Dr. Zamvil has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Horizon. The institution of Dr. Zamvil has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for AAN. The institution of Dr. Zamvil has received research support from Sumaira Foundation. Dr. Zamvil has received personal compensation in the range of $5,000-$9,999 for serving as a Advisory Board with Genzyme. Dr. Zamvil has received personal compensation in the range of $500-$4,999 for serving as a Advisory Board with Genentech. Dr. Zamvil has received personal compensation in the range of $500-$4,999 for serving as a Advisory Board with Alexion.