ORIGINAL PAPER Patterns of constitutive and IFN-γ inducible expression of HLA class II molecules in human melanoma cell lines T. Rodríguez & R. Méndez & A. Del Campo & N. Aptsiauri & J. Martín & G. Orozco & G. Pawelec & D. Schadendorf & F. Ruiz-Cabello & F. Garrido Received: 21 July 2006 / Accepted: 19 October 2006 / Published online: 20 December 2006 # Springer-Verlag 2006 Abstract Major histocompatibility complex (MHC) class II proteins (HLA-DR, HLA-DP and HLA-DQ) play a fundamental role in the regulation of the immune response. The level of expression of human leukocyte antigen (HLA) class II antigens is regulated by interferon-γ (IFN-γ) and depends on the status of class II trans-activator protein (CIITA), a co-activator of the MHC class II gene promoter. In this study, we measured levels of constitutive and IFN-γ- induced expression of MHC class II molecules, analysed the expression of CIITA and investigated the association between MHC class II transactivator polymorphism and expression of different MHC class II molecules in a large panel of melanoma cell lines obtained from the European Searchable Tumour Cell Line Database. Many cell lines showed no constitutive expression of HLA-DP, HLA-DQ and HLA-DR and no IFN-γ-induced increase in HLA class II surface expression. However, in some cases, IFN-γ treatment led to enhanced surface expression of HLA-DP and HLA-DR. HLA-DQ was less frequently expressed under basal conditions and was less frequently induced by IFN-γ. In these melanoma cell lines, constitutive surface expression of HLA-DR and HLA-DP was higher than that of HLA-DQ. In addition, high constitutive level of cell surface expression of HLA-DR was correlated with lower inducibility of this expression by IFN-γ. Finally, substitu- tion A→G in the 5′ flanking region of CIITA promoter type III was associated with higher expression of constitu- tive HLA-DR (p<0.005). This study yielded a panel of melanoma cell lines with different patterns of constitutive and IFN-γ-induced expression of HLA class II that can be used in future studies of the mechanisms of regulation of HLA class II expression. Keywords HLA class II . Melanoma . CIITA . Polymorphism Introduction Major histocompatibility complex (MHC) class I and II products play a central role in immune system function by restricting T cell recognition of foreign antigens (Ags) processed as small peptides. In many cases, the aim of cancer immunotherapy is to stimulate T cell responses against tumour-specific proteins. In the past, CD8+ cyto- lytic T lymphocytes (CTLs) were implicated as the main Immunogenetics (2007) 59:123–133 DOI 10.1007/s00251-006-0171-9 T. Rodríguez : R. Méndez : A. Del Campo : N. Aptsiauri : F. Ruiz-Cabello : F. Garrido (*) Departamento de Análisis Clínicos, Hospital Universitario Virgen de las Nieves, Universidad de Granada, Avda. Fuerzas Armadas 2, 18014 Granada, Spain e-mail: federico.garrido.sspa@juntadeandalucia.es J. Martín : G. Orozco Instituto de Parasitología y Biomedicina “López Neyra”, Granada, Spain G. Pawelec Section for Transplantation Immunology and Immunohaematology, Zentrum für Medizinische Forschung, Waldhörnlestr.22, 72072 Tübingen, Germany D. Schadendorf Skin Cancer Unit of the German Cancer Research Center, University Hospital Mannheim, Mannheim, Germany