Genetic background and T-cell expansion have been confirmed as the most important factors leading to psoriasis susceptibility in the Caucasian population. This study was performed to identify the T-cell receptor Vβ repertoire and HLA-Cw genotype in twenty Mexicans of two different ethnicities with severe chronic plaque-type psoriasis. HLA-Cw typing was performed to detect the allele pattern by SSP-PCR. In parallel, RT-PCR and Western blot were used for the identification of the TCR Vβ expression in peripheral blood cells. We identified a variety of HLA-Cw alleles in this group of patients distinct from the widely known HLA-Cw 0602 Caucasian allele. Moreover, TCR Vβ-2 and Vβ-7 clone-type frequencies were different and statistically significant (P = 0.0280). We speculate that because of diverse genetic backgrounds, the susceptibility to disease and activation of T-cells for a proper immune response could be specific; therefore, the findings might contribute to the elucidation of the pathogenesis in psoriatic Mexican patients.