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Administration of PLP_139–151 Primes T Cells Distinct from Those Spontaneously Responsive In Vitro to This Antigen¹

Romina Penitente^*, Chiara Nicolò^*, Peter Van den Elzen, Gabriele Di Sante^*, Chiara Agrati, Francesca Aloisi, Eli E. Sercarz^¶ and Francesco Ria^2,*

^* Institute of General Pathology, Catholic University, Rome; National Institute for Infectious Diseases "Lazzaro Spallanzani" Istituto Di Ricovero e Cura a Carattere Scientifico, Rome; Department of Cell Biology and Neuroscience, Istituto Superiore di Sanità, Rome, Italy; Department of Pathology and Laboratory Medicine, University of British Columbia, British Columbia Children and Women’s Hospital, Vancouver, British Columbia, Canada; and ^¶ Torrey Pines Institute for Molecular Studies, San Diego, CA 92121

We examined the TCR repertoire used by naive SJL mice in their in vitro spontaneous response to proteolipid protein (PLP) 139–151 by Vβ-Jβ spectratyping and compared it to that used after immunization with the peptide. T cells from immunized mice use the public rearrangement Vβ10-Jβ1.1, but naive mice do not; in contrast, TCR CDR3-β rearrangements of Vβ18-Jβ1.2 and Vβ19-Jβ1.2 consistently are associated with the spontaneous response. T cells involved in spontaneous and induced responses can each recognize PLP_139–151 presented in vivo, but its s.c. administration has different consequences for the two repertoires. Four days after immunization, T cells associated with spontaneous responsiveness appear in the draining lymph nodes but disappear by day 10 and never appear elsewhere. Simultaneously, Vβ10-Jβ1.1 T cells are likewise activated in the lymph nodes by day 4 and spread to the spleen by day 10. Eight- to 10-wk-old naive mice use a narrower repertoire of TCRs than do immunized age-matched mice. Induced Vβ10-Jβ1.1 T cells home to the CNS during experimental autoimmune encephalomyelitis, whereas we failed to detect Vβ18-Jβ1.2 and Vβ19-Jβ1.2 TCR rearrangements in the CNS. Thus, we observe that administration of PLP_139–151 primes a T cell repertoire distinct from the one responsible for spontaneous responsiveness. This "immunized" repertoire substitutes for the naive one and becomes dominant at the time of disease onset.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by grants from the Italian Foundation for Multiple Sclerosis (2003/R/46) and from the Italian Ministry for University and Research (FIRB RBNEO14BML) to F.R., and by grants from the Multiple Sclerosis National Research Institute and National Institutes of Health (AI-42396) to E.E.S. C.N. is supported by a research fellowship from the Italian Foundation for Multiple Sclerosis.

² Address correspondence and reprint requests to Dr. Francesco Ria, Catholic University, Largo Francesco Vito 1, 00168 Rome, Italy. E-mail address: fria{at}rm.unicatt.it

³ Abbreviations used in this paper: R-EAE, relapsing experimental autoimmune encephalomyelitis; b, base; DC, dendritic cell; LN, lymph node; LNC, lymph node cells; p139, proteolipid protein peptide 139–151; p178, proteolipid protein peptide 178–191; PLP, proteolipid protein; RSI, relative stimulation index.