We used the human processing defective cell line 174CEM.T2 (T2) to identify potential cytotoxic T lymphocyte (CTL) epitopes of human proteins. Exogenously added peptides can increase the number of properly folded HLA‐A2.1 molecules on the cell surface of T2 cells, as shown by immunofluorescence measurements using the mouse monoclonal antibody BB7.2 (anti‐HLA‐A2.1) and fluorescein isothiocyanate‐labeled goat anti‐mouse F(ab')2 antibody. The peptides were selected on the basis of a computer score derived from the recently described HLA‐A2.1 specific motif. Analysis of the influenza matrix protein showed that 15 out of 35 high‐scoring peptides up‐regulate the expression of HLA‐A2.1 molecules on theT2 cell surface. The combination of the computer scoring program and an immunofluorescence‐based peptide binding assay allows rapid detection of potential CTL target peptides.
Minor Histocompatibility (mH) antigens are polymorphic endogenously synthesized products that can be recognized by alloreactive T cells in the context of major histocompatibility complex molecules. In transplant situations where tissue donor and recipient are matched for HLA, mH antigens may trigger strong cellular immune responses. To gain insight into the polymorphism of mH antigens we studied their frequencies in the healthy population. Five HLA class I restricted mH antigens recognized by distinct cytotoxic T-cell (CTL) clones were used in the population genetic analysis consisting of a panel (N = 100) of HLA typed target cells. Three mH antigens showed phenotype frequencies of 69 % or higher, this contrasted the frequencies of two other mH antigens with 16 and 7% respectively. To gain insight into the "functional" polymorphism of the T-cell response to mH antigens, we analyzed the specificity of CTL clones within individuals. Three out of five individuals investigated shared a CTL response to one single HLA-A2 restricted mH antigen. These results indicate limited allelic polymorphism for some mH antigens in the healthy population and are suggestive of the existence of immunodominant human mH antigens.
The association between HLA–DR antigens and rheumatoid arthritis (RA) was investigated in a wellcharacterized cohort of RA patients who were followed from the beginning of the disease (mean followup 6 years). The frequencies of HLA–DR antigens in patients with possible or probable RA (n = 49) were similar to those in controls. In patients with definite RA (n = 134), the frequencies of DR1, DR4, and DRw53 were increased, whereas the frequencies of DR2, DR3, DRw6, DRw13, and DRw52 were decreased, compared with controls. Comparison of HLA–DR frequencies in patients with definite RA subclassified according to the severity of the disease at the end of the followup period revealed a difference only in the frequency of DR4, which was increased in patients with progressive RA (59.2%) compared with those who had mild RA (34.8%). Further analysis showed that, compared with DR4‐negative RA patients, DR4‐positive patients had more swollen joints, higher scores on the Ritchie articular index, the Health Assessment Questionnaire, and the Steinbrocker functional classification, more radiologic abnormalities, and more use of second‐line drugs. Also, the rate of progression of radiologic abnormalities, functional classification, and use of second‐line drugs was higher in DR4‐positive patients. We conclude that DR4 is associated with a more severe disease course, and is a prognostic marker in early RA.
Clinicians should be alert for early skin lesions within the complete nasociliary dermatome, because they are a reliable prognostic sign of sight-threatening ocular complications in acute herpes zoster ophthalmicus.
The results of analyses of 1218 consecutive corneal transplants performed in a single centre reveal that the most important prognostic factors for corneal allograft survival are recipient corneal vascularisation, graft diameter, HLA-A and B matching especially for high risk patients, organ culture storage of donor corneas prior to transplantation and donor age.
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