RESUMO
Algorithms derived from measurements of short-peptide (8-10 mers) binding to class I MHC proteins suggest that the binding groove of a class I MHC protein, such as K(b), can bind well over 1 million different peptides with significant affinity (<500 nM), a level of ligand-binding promiscuity approaching the level of heat shock protein binding of unfolded proteins. MHC proteins can, nevertheless, discriminate between similar peptides and bind many of them with high (nanomolar) affinity. Some insights into this high-promiscuity/high-affinity behavior and its impact on immunodominant peptides in T-cell responses to some infections and vaccination are suggested by results obtained here from testing a model developed to predict the number of cell surface peptide-MHC complexes that form on cells exposed to extracellular (exogenous) peptides.
Assuntos
Antígenos de Histocompatibilidade Classe I/genética , Animais , Sítios de Ligação , Membrana Celular/metabolismo , Endocitose , Genes MHC Classe I , Humanos , Concentração Inibidora 50 , Cinética , Ligantes , Camundongos , Modelos Biológicos , Ovalbumina/química , Peptídeos/química , Ligação Proteica , Desnaturação Proteica , Dobramento de Proteína , Linfócitos T/imunologiaRESUMO
The clinical evaluation of athletes during symptom evaluation or pre-participation screening often involves interpretation of the 12-lead electrocardiogram (ECG). Differentiating abnormal ECG findings suggestive of underlying cardiovascular disease from benign findings caused by exercise-induced cardiac adaptations can be challenging, and recent clinical guidelines have been created for this purpose. One of the most common ECG findings in athletes is the early repolarization pattern (ERP), characterized by diffuse J-point elevation and concave ST-segment elevation, and long regarded as a normal variant. However, recently published data suggest that the ERP may be a marker of increased risk for sudden cardiac death (SCD) in the general population. The observation that the ERP can indicate increased SCD risk has important implications for the clinician charged with the care of athletes. This review will describe the evolving understanding of the ERP and will explore the relevance of the ERP for the care of athletes.