Kevin H. Kim

HLA Class I Binding Promiscuity of the CD8 T-Cell Epitopes of Human Papillomavirus Type 16 E6 Protein

ABSTRACT One of the critical steps in the progression to cervical cancer appears to be the establishment of persistent human papillomavirus (HPV) infection. We have demonstrated that the lack of cytotoxic T-lymphocyte response to HPV type 16 (HPV 16) E6 protein was associated with persistence and that the potential presence of dominant CD8 T-cell epitopes was most frequently found (n = 4 of 23) in the E6 16-40 region by examining the pattern of CD8 T-cell epitopes within the E6 protein in women who had cleared their HPV 16 infections. The goal of this study was to define the minimal/optimal amino acid sequences and the HLA restricting molecules of these dominant CD8 T-cell epitopes as well as those of subdominant ones if present. Three dominant epitopes, E6 29-38 (TIHDIILECV; restricted by the HLA-A0201 molecule), E6 29-37 (TIHDIILEC; restricted by B48), and E6 31-38 (HDIILECV; restricted by B4002), and one subdominant epitope, E6 52-61 (FAFRDLCIVY; restricted by B35) were characterized. Taken together with a previously described dominant epitope, E6 52-61 (FAFRDLCIVY; restricted by B57), the CD8 T-cell epitopes demonstrated striking HLA class I binding promiscuity. All of these epitopes were endogenously processed, but the presence of only two of the five epitopes could have been predicted based on the known binding motifs. The HLA class I promiscuity which has been described for human immunodeficiency virus may be more common than previously recognized.

Different Methods of Identifying New Antigenic Epitopes of Human Papillomavirus Type 16 E6 and E7 Proteins

ABSTRACT Human papillomavirus (HPV) infection is the most common cause of sexually transmitted viral infection and is the main cause of cervical cancer. Identification of HPV T-cell epitopes would be instrumental not only in our understanding of the protective immune response but also in the development of vaccines and immunotherapies. In contrast to viruses which cause systemic infection, identification of HPV epitopes is technically challenging because HPV causes a localized mucosal infection and the frequency of pathogen-specific T lymphocytes in peripheral blood is expected to be low. Here we describe three new antigenic epitopes (E7 7-15 [TLHEYMLDL], E6 52-61 [FAFRDLCIVY], and E7 79-87 [LEDLLMGTL]) of HPV 16 E6 and E7 proteins which have oncogenic activities. E7 7-15 was identified among peptides previously shown to bind to human leukocyte antigen (HLA)-A2.1 molecule, but it was found likely to be restricted by the HLA-B48 molecule. E6 52-61 (likely to be restricted by HLA-B57) and E7 79-87 (likely to be restricted by HLA-B60) were detected, based on the magnitude of the T-cell immune responses, in another individual. In particular, T-cell clones specific for the E6 52-61 epitope were isolated effectively by magnetically selecting them based on gamma interferon secretion. This is an efficient method of identifying new epitopes of antigens for which the number of specific T lymphocytes in the circulation is expected to be small, and it should be widely applicable in identifying new T-cell epitopes.

Phase 1 clinical trial of intralesional injection of Candida antigen for the treatment of warts.

ten at an appropriate literacy level to ensure maximum comprehension. Other nonpharmacologic adherence strategies include empowering support staff to provide face-to-face patient counseling, which will likely lead to increased adherence and save physicians’ time. Another strategy is encouraging patients to self-monitor medication adherence. Asking patients to keep a medication diary and bring back medication tubes at each visit may also promote greater adherence. Strong evidence exists in adherence literature that a complicated medication regimen is associated with lower adherence. To increase adherence, dermatologists need to consider designing regimens with the fewest possible number of medications and the lowest dosing frequency. While medications with combined formulations are often more costly, this increased cost may be justified for selected patients if it significantly improves adherence and prevents unnecessary office visits resulting from nonadherence. To close this practice gap, dermatologists need to address the issue of medication adherence explicitly with their patients, their medical staff, and themselves. While changes in existing practices may be difficult to implement, increasing patient adherence is a worthwhile effort at the heart of effective therapeutics.

Patterns of CD8 T-Cell Epitopes within the Human Papillomavirus Type 16 (HPV 16) E6 Protein among Young Women Whose HPV 16 Infection Has Become Undetectable

ABSTRACT The patterns of CD8 T-cell epitopes recognized within the E6 protein in women who had cleared their human papillomavirus 16 infection were examined. T-cell lines were established using autologous dendritic cells infected with a recombinant vaccinia virus. Evidence of potential antigenic epitopes was shown in 8 of 23 (34.8%) women.

Dermatitis herpetiformis presenting as pseudovasculitis

DH: dermatitis herpetiformis DIF: direct immunofluorescence EED: erythema elevatum diutinum INTRODUCTION Dermatitis herpetiformis (DH) is a cutaneous manifestation of gluten intolerance characterized by an intensely pruritic, papulovesicular eruption with a predilection for the extensor extremities, scalp, and buttocks. Because of its variable clinical presentation, DH can be a challenging clinical diagnosis. However, histopathology and immunofluorescence can provide vital data in confirming the diagnosis. We report a case of a 47-year-old patient who presented with clinical features resembling vasculitis but with classic histopathology and immunofluorescence findings for DH.

Detection of Human Papillomavirus Type 16-Specific T Lymphocytes by a Recombinant Vaccinia Virus-Based Enzyme-Linked Immunospot Assay

ABSTRACT Cell-mediated immunity, particularly that induced by T cells, is thought to have a key role in controlling infection. The enzyme-linked immunospot (ELISPOT) assay has been successfully adapted to detect T-cell immune response to a variety of pathogens. However, it still remains a challenge to detect antigen-specific T cells when the numbers of circulating cells are low, such as in a local cervical infection caused by genital human papillomavirus (HPV). The goal of this study was to develop a protocol for enhanced detection of HPV-specific CD8+ T cells by examining a number of the variables involved in performing an ELISPOT assay. Since blood samples consistently positive for HPV-specific T cells are difficult to obtain, previously described human papillomavirus type 16 (HPV16) E6 52-61 (FAFRDLCIVY)-specific T-cell clone cells (13) seeded in peripheral blood mononuclear cells from an HLA-B57-positive blood donor were used. The variables examined were the amounts of primary and secondary anti-gamma interferon antibodies, amounts of antigen-presenting monocytes and recombinant vaccinia virus expressing the HPV16 E6 protein, and amounts of exogenous cytokines added (recombinant human interleukin-2 [rhIL-2] and rhIL-7). The amounts of antigen-presenting monocytes, followed by the concentration of exogenous rhIL-2, had the most pronounced and significant effects in enhancing sensitivity of the ELISPOT assay. Blood samples from six patients being monitored for abnormal Pap smear results and from 12 healthy volunteers were examined using the enhanced conditions.

Noninfectious Peritoneal Dialysis Exit Site Rash—An Unusual Case Report and Review of the Literature

Mohammed Siddiqui, Loretta Bradford, Jennifer Kaley, Gina Johnson, Kevin H. Kim, Kristen Addis and Manisha Singh Division of Nephrology, Department of Internal Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA; Department of Dermatology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA; VA, Central Arkansas Veterans Healthcare System, Little Rock. Arkansas, USA; and Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA

Eruptive xanthogranuloma in a healthy adult male

Xanthogranuloma is a benign, non‐Langerhans cell histiocytosis primarily diagnosed in infants and children, although a subset occurs in adults. Multifocal eruptive presentation of xanthogranuloma is very rare with only 4 previous cases reported in the literature to our knowledge. We describe a case of eruptive xanthogranuloma in a 49‐year‐old man who presented with sudden onset of numerous asymptomatic, red‐yellow to orange papules on the face, scalp, axilla, flank and scrotum. Histologic features were consistent with xanthogranuloma with diffuse mixed infiltrate of foamy histiocytes, Touton giant cells and lymphocytes. Other than temporarily elevated non‐fasting triglycerides, lab values have been unremarkable including serum plasma electrophoresis; however, the patient will continue to be monitored for ocular and other extracutaneous involvement and hematologic malignancies.