Proteasomal cleavage does not determine immunogenicity of gp100-derived peptides gp100 209-217 and gp100 209-217T210M.

Immune responses against tumor-associated antigens rely on efficient epitope presentation. The melanoma-associated antigen (Ag) gp100 contains HLA-A*0201 ligands that are characterized by low to medium binding affinity, among which gp100(209-217) is the most prominent (Kawakami et al., J Immunol 154:3961-3968, 1995). While this epitope is a natural T-cell target, it primes with low-efficiency T-cell responses during immunization. A modified gp100 epitope, gp100(209-217T210M), that contains a Thr to Met substitution at position 2 of the antigenic nonamer is characterized by high binding affinity for HLA-A*0201 and elicits strong and clinically effective T-cell responses. This higher affinity is believed to represent the sole reason for enhanced immunogenicity. Contrasting with this observation is the unpredictable relationship between affinity and immunogenicity observed in other antigen systems. In addition, we noted a striking difference between the capability of endogenously processed gp100(209-217) and gp100(209-217T210M) to induce T-cell responses in an in vitro model. Therefore, we questioned whether factors other than HLA-affinity might play a role in determining the immunogenicity of these epitopes. In the present study, we evaluated the in vitro proteasomal cleavages of 23meric precursor peptides encompassing the native sequence (gp100(201-223)) or the modified sequence (gp100(201-223T210M)). Here we show that the standard proteasome liberates the C-termini of both antigenic peptides but not the N-termini. Quantitative analysis of the digestion products revealed that more of the fragments displaying the final C-termini were produced from the wild-type precursor. However, a stronger TCR engagement was observed when fractions of digested gp100(201-223T210M) were used to activate an HLA-A*0201-expressing target T-cell clone. This difference was also found using separately produced, synthetic nonamers. In conclusion, the high binding affinity of gp100(209-217T210M) seems to compensate for possible differences in proteasomal cleavage at the biological level. Since the final antigenic nonamer is not directly produced by the proteasome, additional further factors may influence the antigenic peptide availability, such as post-proteasomal processing and intracellular peptide transport.

Pavement Surface on Macadam Base, Adair County, HR-209, Construction Report, 1980

The objectives were to determine the feasibility and performance of this type of construction and to determine if the macadam base is effective in reducin9or eliminating D-cracking deterioration.

Français 209

Contient : 1° « Gratianopolitanae urbis descriptio a LAURENTIO RABOTIO et PETRO GILIBERTO, senatoribus gratianopolitanis, 1572 » ; 2° « Inscriptiones duae quae Valentiae extant » ; 3° « Descriptio urbis Valentinae, versibus expressa ab eodem PETRO GILIBERTO » ; 4° « Ejusdem PETRI GILIBERTI de Gasparis Colignii acerba et improvisa morte carmen » ; 5° « Sommaire de ce que j'ay peu trouver de Valence sur le Rhodne ». (Extrait de Me MEDARD DU CLUSET) ; 6° « Extrait d'un livre fort ancien escript à la main en parchemin, de lettre fort caduque, estant en la possession de noble Clement Faure de Valence, avec autres extraits de STRABON, OROSE, PTOLEMEE, etc. » ; 7° « De la Cité de Valence sur le Rhone, selon Me FRANÇOIS ROALDES »

Resolución N° 209 ¿Cómo entiende la Cámara de comercio el evento de suspensión de deliberaciones en una asamblea de accionistas respecto del tiempo que estas se pueden suspender sin que la reunión pierda validez legal?

Servicios registrales

Resolución N° 209 ¿Cómo estudia la cámara de comercio el elemento del quórum en las reuniones de asamblea en una sociedad en comandita por acciones?

Servicios registrales

Precision laser spectroscopy of the ground state hyperfine splitting of hydrogenlike ^209 Bi^82+

The first direct observation of a hyperfine splitting in the optical regime is reported. The wavelength of the M1 transition between the F = 4 and F = 5 hyperfine levels of the ground state of hydrogenlike ^209 Bi^82+ was measured to be \lamda_0 = 243.87(4) nm by detection of laser induced fluorescence at the heavy-ion storage ring ESR at GSI. In addition, the lifetime of the laser excited F = 5 sublevel was determined to be \tau_0 = 0.351(16) ms. The method can be applied to a number of other nuclei and should allow a novel test of QED corrections in the previously unexplored combination of strong magnetic and electric fields in highly charged ions.

Acuerdo No. 209

Consagración de Colegiales de Número del COlegio Mayor de Nuestra Señora del Rosario. 3 de diciembre de 2009

O jogo das interligadas: uma política pública em avaliação: a lei no. 10.209/86 do município de São Paulo: 1986-1993

Trata dos problemas de operacionalização da Lei Municipal n. 10.209 de 09 de dezembro de 1986, de seu aperfeiçoamento de 1988 a 1993 e dos resultados obtidos em habitações de interesse social doadas a Prefeitura pelos empreendedores imobiliários, em contrapartida a exceções à legislação de uso e ocupação do solo do Município de São Paulo.