Showing papers by "Sandra O. Gollnick published in 2008"

Differential contribution of TAP and tapasin to HLA class I antigen expression

Abstract: Expression of class I human leucocyte antigens (HLA) on the surface of malignant cells is critical for their recognition and destruction by cytotoxic T lymphocytes. Surface expression requires assembly and folding of HLA class I molecules in the endoplasmic reticulum with the assistance of proteins such as Transporter associated with Antigen Processing (TAP) and tapasin. Interferon-γ induces both TAP and tapasin so dissection of which protein contributes more to HLA class I expression has not been possible previously. In this study, we take advantage of a human melanoma cell line in which TAP can be induced, but tapasin cannot. Interferon-γ increases TAP protein levels dramatically but HLA class I expression at the cell surface does not increase substantially, indicating that a large increase in peptide supply is not sufficient to increase HLA class I expression. On the other hand, transfection of either allelic form of tapasin (R240 or T240) enhances HLA-B*5001 and HLA-B*5701 antigen expression considerably with only a modest increase in TAP. Together, these data indicate that in the presence of minimal TAP activity, tapasin can promote substantial HLA class I expression at the cell surface.

Photopheresis in HIV-1 infected patients utilizing benzoporphyrin derivative (BPD) verteporfin and light.

Abstract: An ex vivo trial utilizing photopheresis with Benzoporphyrin Derivative as the photoactive compound, identified the minimum energy levels of light and concentrations of BPD that eradicated both cell-free and cell-associated HIV-1 infectivity without destroying the virus particles or infected leukocytes. Leukocytes remained viable with altered chemokine/cytokine expression. Apoptosis was induced in a minority of CD4 but not CD8 positive cells with a statistically significant increase in cytolytic T-cell activity. In the 24 week clinical trial in 7 HIV-1 infected patients, three who had rapidly rising viral loads prior to initiating therapy stabilized. Two had a sustained greater than 0.5 log decrement and 5 had stable plasma viral loads (less than a 0.5 log increment or decrement) with varied effects on absolute CD4 and CD8 positive lymphocytes counts. One achieved a greater than 1 log decrement in HIV-1 plasma viral load and undetectable in vivo cell-free and cell-associated HIV-1 infectivity with an increased in vitro lymphocyte mitogen stimulation index. Under amended protocol, 5 additional 12 month courses were administered to three additional patients and two of the previous enrollees. Area under the curve for viral load showed a significant decrease from pre- to post-therapy (p 0.007). No associated toxicities were observed.