RESUMO
Thymocytes are positively selected for alphabeta T cell antigen receptors (TCR) that recognize antigen in conjunction with self-major histocompatibility complex (MHC) molecules. MHC bound peptides participate in positive selection; however, their role has remained controversial. A TCR transgenic mouse was established using a TCR restricted to the MHC class Ib molecule, H2-M3. Having defined H2-M3 as the positively selecting MHC molecule, the severely limited number of H2-M3 binding peptides allowed us to characterize an NADH dehydrogenase subunit 1 (ND1)-derived peptide as the physiological ligand of positive selection. This peptide bears no apparent sequence homology to the cognate peptide, is expressed ubiquitously, and yet does not interfere with peripheral T cells. Our studies also suggest that positive selection becomes promiscuous at high epitope densities.
Assuntos
Antígenos H-2/genética , Antígenos de Histocompatibilidade Classe I/genética , Receptores de Antígenos de Linfócitos T alfa-beta/genética , Animais , Apresentação de Antígeno/genética , Linhagem Celular , Cruzamentos Genéticos , Feto , Antígenos H-2/metabolismo , Antígenos de Histocompatibilidade Classe I/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , N-Formilmetionina/imunologia , N-Formilmetionina/metabolismo , NADH Desidrogenase/imunologia , NADH Desidrogenase/metabolismo , Oligopeptídeos/imunologia , Oligopeptídeos/metabolismo , Técnicas de Cultura de Órgãos , Receptores de Antígenos de Linfócitos T alfa-beta/metabolismo , Subpopulações de Linfócitos T/citologia , Subpopulações de Linfócitos T/metabolismo , Células Tumorais CultivadasRESUMO
Thermal burns as well as hyperbaric oxygen (HBO) may cause immuno-suppression. This is one of the reasons why there is some controversy in the literature regarding adjuvant HBO treatment for thermal burn patient, despite the fact that HBO is known to decrease edema formation and possibly inhibits the progression from second to third degree burns. In this study, lymphocyte subpopulations were labelled with monoclonal antibodies W3/25 for helper cells, and OX-8 for cytotoxic/suppressor cells, to determine changes following early burn wound excision and acute or chronic HBO treatment in a 10% full-thickness burn model in rats. Lymphocyte subpopulations were extracted from blood and spleen on day 1, 8, and 15 following burn and/or treatment. W3/25 cells did not show any significant changes in blood or spleen over time. Significantly lower OX-8 cell counts were found in the group with burn + excision + chronic HBO treatment on day 8 and 15. Acute or chronic HBO treatment alone did not produce evidence of immuno-suppression.
