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Neonatally Primed Lymph Node, but Not Splenic T Cells, Display a Gly-Gly Motif within the TCR -Chain Complementarity-Determining Region 3 That Controls Affinity and May Affect Lymphoid Organ Retention¹

Jacque C. Caprio-Young^2,3,, J. Jeremiah Bell^2,*,, Hyun-Hee Lee^*,, Jason Ellis^*, Danielle Nast^*, Gary Sayler, Booki Min and Habib Zaghouani^4,*,

^* Department of Molecular Microbiology and Immunology, University of Missouri School of Medicine, Columbia, MO 65212; Department of Microbiology, University of Tennessee, Knoxville, TN 37996; and Department of Immunology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195

Ig-proteolipid protein 1 (Ig-PLP1) is an Ig chimera expressing the encephalitogenic PLP1 peptide corresponding to amino acid residues 139–151 of PLP. Newborn mice given Ig-PLP1 in saline on the day of birth and challenged 7 wk later with PLP1 peptide in CFA develop an organ-specific neonatal immunity that confers resistance against experimental allergic encephalomyelitis. The T cell responses in these animals are comprised of Th2 cells in the lymph node and anergic Th1 lymphocytes in the spleen. Intriguingly, the anergic splenic T cells, although nonproliferative and unable to produce IFN- or IL-4, secrete significant amounts of IL-2. Studies were performed to determine whether the two populations display any structural differences in the TCR H chain variable region that could contribute to the differential affinity and retention in different organs. Responsive Th2 lymph node T cells and anergic splenic lymphocytes were immortalized, and the structures of their TCR V were determined. The results show that V and J usage was random, but the CDR3 regions of the lymph node cells had a conserved Gly-Gly motif. Analysis of TCR affinity/avidity correlated the Gly-Gly motif with lower affinity and retention of the Th2 cells in the lymph node. Also, it is suggested that a higher TCR affinity may be a contributing factor for the development of the neonatal Th1 response in the spleen.

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