The purpose of these studies was to identify HLA-A2+ immunogenic peptides derived from XBP1 antigens to induce a multiple myeloma (MM)-specific immune response. Six native peptides from non-spliced XBP1 antigen and three native peptides from spliced XBP1 antigen were selected and evaluated for their HLA-A2 specificity. Among them, XBP1184–192, XBP1 SP196–204 and XBP1 SP367–375 peptides showed the highest level of binding affinity, but not stability to HLA-A2 molecules. Novel heteroclitic XBP1 peptides, YISPWILAV or YLFPQLISV, demonstrated a significant improvement in HLA-A2 stability from their native XBP1184–192 or XBP1 SP367–375 peptide, respectively. Cytotoxic T lymphocytes generated by repeated stimulation of CD3+ T cells with each HLA-A2-specific heteroclitic peptide showed an increased percentage of CD8+ (cytotoxic) and CD69+/CD45RO+ (activated memory) T cells and a lower percentage of CD4+ (helper) and CD45RA+/CCR7+ (naïve) T cells, which were distinct from the control T cells. Functionally, the CTLs demonstrated MM-specific and HLA-A2-restricted proliferation, IFN-γ secretion and cytotoxic acivity in response to MM cell lines and importantly, cytotoxicty against primary MM cells. These data demonstrate the distinct immunogenic characteristics of unique heteroclitic XBP1 peptides which induce MM-specific CTLs and highlights their potential application for immunotherapy to treat the patients with MM or its pre-malignant condition.

Bone microstructure reflects the rate of bone tissue deposition. That hypothesis [1] was recently tested experimentally [2-4]. Rapidly growing bones have a greater proportion of vascular canals than slowly growing bones do. In addition, bones experiencing relatively high growth rates form radial vascular canals. Those radial canals radiate outwards from the periosteal surface and allow rapid increases in bone girth. Whether the deposition of radials canals plays a role in evolutionary increases in body size, however, remains untested.

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Background: Eotaxins are CC chemokines implicated in the development of eosinophilic inflammation in asthma. In airway epithelial lines, expression of eotaxin−2 is induced through activation of IL−4Ra by a STAT6 mechanism; however it is not induced by IL−13 in primary human epithelial cells. In fresh epithelial cells, eotaxin−3 mRNA expression correlates with asthma severity and iNOS mRNA (Trudeau ATS 2006). Similar studies have not been done for eotaxin−1 or eotaxin−2. The study's objective was to characterize expression of eotaxin−1 and 2 by fresh airway epithelial cells from asthma subjects of varying severity and normal subjects. Methods: Fresh cells were obtained from bronchial brushings of 4 NC and 13 asthmatic subjects. Eotaxin−1 and 2 mRNA expression was quantified by real time PCR, normalized to GAPDH. FEV−1/ FVC was measured by spirometry. Sputum eosinophil percentages were obtained by dividing the number of eosinophils by total white blood cells. Results: Eotaxin−2 mRNA expression was generally higher in asthmatics than NC [(mean 0.20 arbitrary units (AU), −SEM 0.14, +SEM 0.29) vs.( 0.04 AU,−SEM 0.02,+SEM 0.08), p=0.056]. Expression tended to increase with disease severity with severe subjects expressing the most eotaxin−2 [(Severe =0.29 AU, −SEM 0.19, +SEM 0.0.44) vs.(Mod/Mild=0.09 AU,−SEM 0.05,+SEM −.15) vs (Normal mean 0.04,−SEM 0.02,+SEM 0.08), p = 0.05]. Eotaxin−2 expression correlated with eosinophils % (rho=0.71, p=0.002), FEV−1/FVC (rho=−0.57, p=0.04), and eotaxin−3 mRNA expression (Rho=0.6, p=0.01). Eotaxin−1 mRNA was not detected in any of the subjects. Conclusion: Both eotaxin−2 and eotaxin 3 expression by human airway epithelial cells may contribute to the airway eosinophilia observed in asthma. Whether both are stimulated by an IL−4R mechanism in vivo, or whether other factors explain the differences seen in vitro and ex vivo requires further study.This abstract is funded by: UL1 RR024153.