The relationship between binding affinity for HLA class I molecules and immunogenicity of discrete peptide epitopes has been analyzed in two different experimental approaches. In the first approach, the immunogenicity of potential epitopes ranging in MHC binding affinity over a 10,000-fold range was analyzed in HLA-A*0201 transgenic mice. In the second approach, the antigenicity of approximately 100 different hepatitis B virus (HBV)-derived potential epitopes, all carrying A*0201 binding motifs, was assessed by using PBL of acute hepatitis patients. In both cases, it was found that an affinity threshold of approximately 500 nM (preferably 50 nM or less) apparently determines the capacity of a peptide epitope to elicit a CTL response. These data correlate well with class I binding affinity measurements of either naturally processed peptides or previously described T cell epitopes. Taken together, these data have important implications for the selection of epitopes for peptide-based vaccines, and also formally demonstrate the crucial role of determinant selection in the shaping of T cell responses. Because in most (but not all) cases, high affinity peptides seem to be immunogenic, our data also suggest that holes in the functional T cell repertoire, if they exist, may be relatively rare.

Little is known about the long-term natural history of Mycobacterium avium complex lung disease (MAC-LD) in untreated patients with stable course. The aim of this study was to investigate the natural course of untreated stable MAC-LD, with a focus on factors associated with clinical deterioration, spontaneous sputum conversion and prognosis. Of 488 patients diagnosed with MAC-LD between 1998 and 2011, 305 patients (62.5%) showed progressive MAC-LD resulting in treatment initiation within 3 years of diagnosis and 115 patients (23.6%) exhibited stable MAC-LD for at least 3 years with a median follow-up duration of 5.6 years. Patients with stable MAC-LD were more likely to have higher body mass index and less systemic symptoms at initial diagnosis compared with patients with progressive MAC-LD, while positive sputum acid-fast bacilli smear, fibrocavitary type and more extensive disease in radiological findings were more associated with progressive MAC-LD. Of the untreated patients with stable MAC-LD, 51.6% underwent spontaneous sputum conversion, with younger age, higher body mass index and negative sputum acid-fast bacilli smear at initial diagnosis found to be predictors of this occurrence. Advanced age, fibrocavitary type and abnormal pulmonary function were negative prognostic factors for survival in patients with stable MAC-LD. Host predisposing factors are relatively more important than microbiological factors in stable MAC-LD patientshttp://ow.ly/nf9N306AQd0