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Adenoviral‐encoded antigens are presented efficiently by a subset of dendritic cells expressing high levels of α v β 3 integrins
Author(s) -
Harui Airi,
Roth Michael D.,
Vira Darshni,
Sanghvi Mihir,
Mizuguchi Hiroyuki,
Basak Saroj K.
Publication year - 2006
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.1105694
Subject(s) - biology , dendritic cell , microbiology and biotechnology , ovalbumin , integrin , antigen , cd11c , major histocompatibility complex , antigen presentation , receptor , t cell , immunology , immune system , gene , biochemistry , phenotype
Dendritic cells (DC) play a central role in antigen presentation and are often targeted by adenoviral (Ad)‐based gene therapy. However, DC lack the coxsackie‐Ad receptor, and little is known about the process by which they acquire and present Ad‐encoded antigens. We examined the expression of α ν β 3 integrins (CD51/CD61) on mouse bone marrow‐derived DC (BM‐DC) and their susceptibility to transduction by Ad vectors. Less than 10% of BM‐DC precursors expressed CD51, but expression increased over time in culture with granulocyte macrophage‐colony stimulating factor (GM‐CSF)/interleukin (IL)‐4. After 7 days, 28 ± 1.7% of CD11c + DC expressed high levels of CD51 (CD51 hi ), and the remaining DC expressed low levels of CD51 (CD51 lo ). CD51 hi CD express higher major histocompatibility complex type 1 (MHC I); however, both of the DC subsets expressed similar levels of MHC II and costimulatory molecules. When exposed to a first‐generation Ad vector, transgene expression was restricted to the CD51 hi DC subset and blocked by soluble peptides expressing an arginine, glycine, aspartic acid (RGD) sequence, confirming the role of integrins in viral entry. Consistent with this, a modified Ad expressing an RGD‐binding sequence in its fiber knob (Ad‐RGD) transduced the CD51 hi DC subset with significantly higher efficiency. When BM‐DC were transduced with an Ad‐expressing ovalbumin (Ad‐OVA), the CD51 hi subset proved superior in activating OT‐I (T cell receptor‐OVA) T cells. Similar to in vitro effects, systemic administration of GM‐CSF/IL‐4 increased the expression of CD51 on splenic DC and rendered these cells susceptible to Ad transduction. These results suggest that a limited subset of DC expressing high levels of α ν β 3 integrins is preferentially transduced by Ad vectors and activates CD8 + T cell responses against Ad‐encoded antigens.